研究者業績

小谷 和彦

コタニ カズヒコ  (Kazuhiko Kotani)

基本情報

所属
自治医科大学 地域医療学センター地域医療学部門  教授
学位
博士(医学)(自治医科大学(JMU))

J-GLOBAL ID
200901036312266574
researchmap会員ID
1000361605

外部リンク

論文

 501
  • Kazuhiko Kotani, Naoki Sakane, Yoshiko Sano, Kokoro Tsuzaki, Yukiyo Matsuoka, Kahori Egawa, Makiko Yoshimura, Chika Horikawa, Yoshinori Kitagawa, Yoshinobu Kiso, Satoshi Kimura, John Schulze, Jennifer Taing, Alejandro Gugliucci
    Journal of Clinical Biochemistry and Nutrition 45(3) 329-334 2009年11月  査読有り筆頭著者責任著者
    Low caloric diet (LCD) is used for weight loss. Paraoxonase 1 (PON-1) is associated with the antioxidant functions of high-density lipoprotein (HDL). Among limited data on the relationships between obesity and PON-1, there has been no study on the effects of a stand-alone LCD on the physiological lactonase activity of PON-1. We investigated the prospective effects of LCD intervention (2 months) for weight loss on serum PON-1 activities (lactonase, arylesterase [mono-esterase] and tri-esterase) and HDL cholesterol (HDL-C), and their association with low-density lipoprotein cholesterol (LDL-C) in overweight and non-morbidly obese but otherwise healthy women (n = 30 mean age, 50.3 years mean body mass index [BMI], 28.5 kg/m2). In addition to the data such as BMI, blood pressure, blood glucose and lipids, PON-1 activities were examined between pre- and post-intervention. The intervention reduced all metabolic outcomes, and PON-1 lactonase activity (determined with 5-[thiobutyl]butyrolactone) significantly decreased by 6.1%, paralleled by arylesterase (by 7.3%) and tri-esterase (by 7.8%). In multiple regression analysis, the percent change of PON-1 lactonase was significantly, positively and independently correlated to that of LDL-C (β = 0.51), HDL-C (β = 0.40), and BMI (β = 0.37). Our results showed that the solo diet treatment on weight loss might reduce serum PON-1 lactonase activity with reduced HDL-C and LDL-C. The relationship between the lactonase and LDL-C may be adaptive, plausibly hypothesizing less need for PON-1 activity as an antioxidant property to protect lipoproteins. Further research is needed to confirm this prediction.
  • Kazuhiko Kotani, Harumi Koibuchi, Toshiyuki Yamada, Nobuyuki Taniguchi
    Clinica Chimica Acta; international journal of clinical chemistry 409(1-2) 67-69 2009年11月  査読有り筆頭著者責任著者
    BACKGROUND: Lifestyle modification improves the pathophysiology of lipid disorder, leading to the development of cardiovascular disease (CVD). While oxidized low-density lipoprotein (oxLDL) may be involved in this mechanism, various oxLDL measurements have recently been developed and therefore further detailed studies are called for in this area. Our aim was to investigate the effects of lifestyle modification on serum amyloid A-LDL (SAA-LDL), a new oxLDL, in subjects with primary lipid disorder. METHODS: A total of 141 asymptomatic subjects (women/men=100/41, mean age 57.6 years) with>or=1 lipid abnormality (circulating high levels of low-density lipoprotein cholesterol [LDL-C] and triglyceride [TG] or low levels of high-density lipoprotein cholesterol [HDL-C]), who completed a 6-month lifestyle modification program in combination with diet and exercise, were analyzed. In the pre- and post-intervention, the metabolic variables including SAA-LDL were assessed. RESULTS: During our intervention, the body mass index, blood pressure, LDL-C, TG, glucose and SAA-LDL significantly decreased, while HDL-C significantly increased. Multiple regression analysis revealed that the change levels of TG (positive) and HDL-C (inverse) were significantly and independently correlated to those of SAA-LDL. CONCLUSIONS: These results suggest that SAA-LDL may contribute to the link between lipid disorder and the development of CVD, and that the application of SAA-LDL measurements may be useful for the assessment of the risk of CVD as a biochemical marker.
  • Mizuho Maekawa, Jiro Kikuchi, Kazuhiko Kotani, Kohjiro Nagao, Tsogbadrakh Odgerel, Kazumitsu Ueda, Mikihiko Kawano, Yusuke Furukawa, Ikunosuke Sakurabayashi
    Atherosclerosis 206(1) 216-222 2009年9月  査読有り
    Tangier disease (TD) is a hereditary disorder characterized by the severe deficiency or absence of high-density lipoprotein cholesterol (HDL-C). TD is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene, most of which are located in the extracellular loops and nucleotide-binding domains. Here we describe the first case of TD carrying a missense mutation in a transmembrane α-helix of ABCA1. A 31-year-old Japanese woman had an extremely low level of HDL-C (1 mg/dl) and yellowish tonsillar swelling, leading to the diagnosis of TD. The proband was homozygous for a point mutation of T4978C in exon 37, which results in the substitution of cysteine-1660 to arginine (C1660R) in the 8th transmembrane segment of ABCA1. Her parents, grandmother, and brother were found to be heterozygous for the same mutation. Both peripheral blood leukocytes from the patient and HEK293 cells transfected with T4978C-mutated ABCA1 normally expressed ABCA1 on the plasma membrane and had normal apolipoprotein A-I-binding ability. However, apolipoprotein A-I-mediated efflux of cholesterol and phospholipids was markedly diminished in HEK293 cells transfected with T4978C-mutated ABCA1. These results suggest that this mutant is normally translated and exists as a stable product with normal localization, yet is functionally defective. Cysteine-1660 appears to be a critical residue for cholesterol transport of ABCA1. © 2009 Elsevier Ireland Ltd. All rights reserved.
  • Alejandro Gugliucci, Kazuhiko Kotani, Jennifer Taing, Yukiyo Matsuoka, Yoshiko Sano, Makiko Yoshimura, Kahori Egawa, Chika Horikawa, Yoshinori Kitagawa, Yoshinobu Kiso, Satoshi Kimura, Naoki Sakane
    Annals of Nutrition and Metabolism 54(3) 197-201 2009年8月  査読有り
    Background: Obesity is a metabolic and cardiovascular risk factor. A low calorie diet (LCD) is one of the treatment modalities for weight loss. Serum advanced glycation end products (AGEs) are linked to increased atherogenicity and inflammation in diseases such as diabetes and renal failure. Obesity has an inflammatory component, but interestingly there are no studies on serum AGE levels in obesity or on the effects of LCD as a therapeutic measure on these markers of glycation. Aim: We hypothesized that weight loss by caloric restriction has a beneficial effect on serum AGE levels. We investigated the prospective effects of a sole LCD intervention for weight loss on serum AGEs in a cohort of overweight and non-morbidly obese but otherwise healthy subjects. Methods: A total of 37 Japanese subjects (30 females, 7 males, mean age 48.2 ± 9.3 years) with a mean BMI of 28.3 ± 3.2 participated in this study. During the intervention period of 2 months, they were placed on an LCD (Diet's™ 5,023 kJ/day) with meal replacement every dinner. The following data were evaluated pre- and post-intervention: AGEs, BMI, waist circumference, blood pressure, serum glucose, cholesterol, triglycerides, HDL- and LDL- cholesterol. Results and Discussion: After the intervention, BMI levels were clearly reduced by 6.3% (p &lt 0.001), waist circumference by 5.7% (p &lt 0.002) and triglycerides by 11.9 % (p &lt 0.002). At baseline, AGEs levels were 63 ± 11 AU for obese subjects and 63 ± 14 for control subjects (not significant). After intervention, AGEs were reduced by 7.21% (range 0-35%, p &lt 0.001). The percent change in AGEs was significantly and positively correlated with that of triglycerides (r = 0.42, p &lt 0.009), waist circumference (r = 0.40, p &lt 0.011), and BMI (r = 0.42, p &lt 0.007). We show for the first time that serum AGEs can be reduced by an LCD intervention on weight loss, a change that correlates with the reduction in triglycerides. This may plausibly be a reflection of a reduction in glycation/lipoxidation due to the caloric restriction and its metabolic consequences, or it may be due to the decreased intake of food containing glycotoxins, or a combination of both. Copyright © 2009 S. Karger AG, Basel.
  • Katsunori Ishida, Masahiko Kato, Yosuke Kato, Kiyotaka Yanagihara, Yoshiharu Kinugasa, Kazuhiko Kotani, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa, Virend K Somers
    Chest 136(1) 125-129 2009年7月  査読有り
    BACKGROUND: C-reactive protein (CRP) is an important risk factor for cardiovascular disease. Furthermore, it has been reported that levels of CRP are increased in patients with obstructive sleep apnea (OSA). The aim of this study was to examine the effects of long-term therapy with nasal continuous positive airway pressure (nCPAP) on CRP levels and to investigate whether compliance with nCPAP therapy more effectively attenuated markers of systemic inflammation in patients with OSA. METHODS AND RESULTS: Fifty-five patients (mean [+/- SEM] age, 55 +/- 2 years; 44 male patients, 11 female patients) with newly diagnosed moderate-to-severe OSA (apnea-hypopnea index > 20 events/h) were studied before and after 6 months of nCPAP treatment. There was a significant reduction in CRP levels after nCPAP therapy (before nCPAP therapy, 0.23 +/- 0.03 mg/dL; after nCPAP therapy, 0.17 +/- 0.02 mg/dL; p < 0.01). Additionally, we divided these patients into two groups based on adherence to nCPAP therapy. A group of patients using nCPAP > 4 h/d and > 5 d/wk were designated as the good compliance group. The decrease in CRP concentration was significant (before nCPAP therapy, 0.23 +/- 0.04 mg/dL; after nCPAP therapy, 0.16 +/- 0.03 mg/dL; p < 0.05) in the good compliance group but not in the poor compliance group (before nCPAP therapy, 0.24 +/- 0.05 mg/dL; after nCPAP therapy, 0.20 +/- 0.05 mg/dL; p = 0.21). Furthermore, we divided those patients into a high CRP group (>/= 0.2 mg/dL) and a normal CRP group (< 0.2 mg/dL) before nCPAP therapy. The significant decrease in CRP levels in the good compliance group was evident only in those patients with an initially elevated CRP level (before nCPAP therapy, 0.48 +/- 0.08 mg/dL; after nCPAP therapy, 0.29 +/- 0.06 mg/dL; p < 0.05). CONCLUSION: Appropriate use of nCPAP in patients with OSA may be required to decrease elevated CRP levels, with possible implications for cardiovascular morbidity and mortality.
  • Kazuhiko Kotani, Noriko Satoh, Yasuhisa Kato, Rika Araki, Kazunori Koyama, Taiichiro Okajima, Makito Tanabe, Mariko Oishi, Hajime Yamakage, Kazunori Yamada, Masakazu Hattori, Akira Shimatsu
    Atherosclerosis 204(2) 526-531 2009年6月  査読有り筆頭著者責任著者
    Background: The putative association between the novel oxidized low-density lipoprotein markers, serum amyloid A-LDL (SAA-LDL) and α1-antitrypsin-LDL (AT-LDL), and obesity and the metabolic syndrome (MetS) has not been previously studied. In the present report, we investigated the levels of SAA-LDL and AT-LDL in relation to the components of the MetS. We also assessed the effect of weight reduction therapy on serum SAA-LDL and AT-LDL levels among obese subjects. Methods: The study population included 421 obese Japanese outpatients (185 men and 236 women, mean age: 51.1 years) enrolled in the multicenter Japan Obesity and Metabolic Syndrome Study (JOMS). The novel oxidized low-density lipoprotein markers, serum SAA-LDL and AT-LDL, were measured in all participants. Results: Circulating SAA-LDL levels were independently associated with the presence and the number of components of the MetS. SAA-LDL levels were also significantly and independently correlated with high-sensitivity C-reactive protein. Notably, successful weight reduction resulted in a significant decrease in circulating SAA-LDL concentrations. Levels of AT-LDL were not associated with the MetS. Conclusions: We documented, for the first time, that serum SAA-LDL levels correlate positively with the number of components of the MetS and weight reduction. Whether SAA-LDL may be involved in the pathophysiology of MetS and atherosclerosis deserves further investigation. © 2008 Elsevier Ireland Ltd. All rights reserved.
  • K. Tsuzaki, K. Kotani, N. Nagai, K. Saiga, Y. Sano, T. Hamada, T. Moritani, M. Yoshimura, K. Egawa, C. Horikawa, Y. Kitagawa, Y. Kiso, N. Sakane
    JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION 32(5) 395-400 2009年5月  査読有り
    Background: In the adiponectin gene polymorphisms, single-nucleotide polymorphism (SNP)-45 and SNP276 have reportedly been associated with obesity, Type 2 diabetes, and other features of metabolic syndrome. Aim: Whether these adiponectin SNP affect obesity-related parameters during caloric restriction in obese subjects. Subjects and methods: Thirty-two obese Japanese women were treated by meal replacement with a low calorie diet for 8 weeks and asked to maintain their habitual lifestyle. Obesity-related parameters were measured before and after the treatment period. We determined four SNP (T45G, I164T, G276T, and C-11377G) using a fluorescent allele-specific DNA primer assay system and FRET probe assay system. Results: After the treatment, the extent of decrease in waist circumference was greater in the subjects with the G/G or G/T genotype of SNP276 than in those with the T/T genotype (p=0.026). As for SNP45, the extent of decrease in triglyceride levels was greater in the subjects with the TIT genotype than in those with the T/G genotype (p=0.003). For SNP-11377, the extent of decrease in systolic blood pressure and fasting plasma glucose was greater in the subjects with the C/G or G/G genotype than in those with the C/C genotype (p=0.044). Conclusion: Our findings indicate that each SNP in the adiponectin gene might modify the change in obesity-related parameters during meal replacement with a low calorie diet. (J. Endocrinol. Invest. 32: 395-400, 2009) (C) 2009, Editrice Kurtis
  • Kazuhiko Kotani, Shinji Fujiwara, Kokoro Tsuzaki, Yoshiko Sano, Yukiyo Matsuoka, Taku Hamada, Naoki Sakane
    Molecular Biology Reports 36(5) 917-920 2009年5月  査読有り筆頭著者責任著者
    Objective Angiotensin II (Ang II), through the Ang II type 2 receptor (AT2R), may play some roles in the pathogenesis of glucose metabolism and diabetes mellitus (DM). The Adenine/Cytosine 3123 (A/C3123) polymorphism in the AT2R gene has reportedly been associated with metabolic conditions such as blood pressure and body mass index (BMI). The present cross-sectional study was aimed at investigating the association between the AT2R gene A/C3123 polymorphism and glycemic control parameters. Methods Among 286 community-dwelling Japanese subjects (men: women = 126:160 mean age, 65.1 years), AT2R A/C3123 polymorphism, which was detected by polymerase chain reaction methods, and metabolic parameters such as blood pressure, BMI, lipoprotein/lipid, insulin, and glycemic control parameters (fasting plasma glucose and HbA1c) were examined. Results In the whole study population, the proportion of C-allele was 67.0% and A-allele was 33.0%. The A-allele carriers had significantly lower HbA1c levels than the C/C-genotyped subjects in the group of women (5.5 ± 0.6 vs. 5.8 ± 1.5%, P = 0.042). The effect on HbA1c persisted to be significant with adjustments to age and BMI. In men, the associations between the polymorphism and glycemic control parameters were non-significantly noted. There were no differences between genotype-based groups in the other metabolic parameters in both sexes. Conclusion These results suggest that the AT2R A/C3123 polymorphism could be a polymorphic marker related to glycemic control, as presented in HbA1c, among general Japanese women. © 2008 Springer Science+Business Media B.V.
  • Kokoro Tsuzaki, Kazuhiko Kotani, Yoshiko Sano, Yukiyo Matsuoka, Kentaro Okazaki, Naoki Sakane
    Journal of Clinical Lipidology 3(1) 59 2009年2月  査読有り
  • Kazuhiko Kotani, Izuru Shioji
    Scandinavian Journal of Clinical and Laboratory Investigation 69(1) 26-27 2009年1月  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Kenji Wakai, Akira Shibata, Yuki Fujita, Itsuro Ogimoto, Mariko Naito, Yoichi Kurozawa, Hiroshi Suzuki, Takesumi Yoshimura, Akiko Tamakoshi, Mitsuru Mori, Fumio Sakauchi, Yutaka Motohashi, Ichiro Tsuji, Yosikazu Nakamura, Hiroyasu Iso, Haruo Mikami, Michiko Kurosawa, Yoshiharu Hoshiyama, Naohito Tanabe, Koji Tamakoshi, Shinkan Tokudome, Shuji Hashimoto, Shogo Kikuchi, Yasuhiko Wada, Takashi Kawamura, Yoshiyuki Watanabe, Kotaro Ozasa, Tsuneharu Miki, Chigusa Date, Kiyomi Sakata, Yoichi Kurozawa, Yoshihisa Fujino, Naoyuki Okamoto, Hideo Shio
    Asian Pacific Journal of Cancer Prevention 10(1) 87-90 2009年  査読有り筆頭著者責任著者
    Evidence suggests a link between adiponectin, an adipocytokine, and liver tumorigenesis. Different multimer complexes of adiponectin, with low-molecular weight (LMW), middle-molecular weight (MMW) and highmolecular weight (HMW), may have different roles. Therefore the present study was performed with the aim of assessing associations between these multimers and liver cancer development. A nested case-control study (59 liver cancer cases [mean age=63.5 years] and 334 controls [62.7 years]) was conducted as a part of the Japan Collaborative Cohort (JACC) Study recruiting healthy participants, aged 40-79 years, for the follow-up period from 1988-1990 to 1999. The end point was liver cancer occurrence/death. Serum levels of HMW, MMW and LMW adiponectin were determined at baseline using an ELISA assay. Multivariate-adjusted logistic regression analyses comparing the tertile levels of adiponectin multimers showed that the groups stratified with the highest percentage of LMW tended to have lower odds ratios (ORs) than the lowest group (OR adjusted for sex, age and area=0.54 [95%CI: 0.26-1.11] and adjusted for sex, age, area, body mass index, smoking, alcohol, coffee consumption, diabetes history and HCV-antibody positivity =0.50 [95%CI: 0.22-1.15]), albeit without statistical significance (set at p&lt 0.05). Higher percentages of circulating LMW adiponectin may lead to a reduction of liver cancer risk and relationships with multimer composition may merit further study.
  • Kazuhiko Kotani, Seiji Adachi, Kokoro Tsuzaki, Naoki Sakane
    Aging Clinical and Experimental Research 21(4-5) 349-352 2009年  査読有り筆頭著者責任著者
    Background and aims: Several studies have examined the associations between measurements used to assess obesity, such as the body mass index (BMI), waist circumference (WC) and intra-abdominal fat area, and cardiometabolic abnormalities. However, the application of these measures in clinical practice requires more detailed examination in older individuals. The abdominal wall fat index (AFI) is ultrasonographically determined via a vertical scan along the upper abdominal median, to measure the maximum thickness of pre-peritoneal fat at the liver surface and the minimum thickness of subcutaneous fat. Few studies, however, have compared the AFI with the BMI as a measure of obesity. Older women were examined to determine the associations among BMI, AFI and cardiometabolic variables. Methods: In 86 asymptomatic women with BMIs of 18.5-29 kg/m2 (mean age±SD 77±6 years mean BMI±SD 22.7±2.5 kg/m2), we measured the following cardiometabolic variables: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), plasma glucose, serum total cholesterol, triglycerides, and high-density lipoprotein cholesterol. Results: In a multiple regression analysis adjusted for all the above cardiometabolic variables, BMI showed a significant negative correlation with age alone, whereas AFI showed a significant positive correlation with DBP and PP. Conclusions: Our results suggest that, compared with BMI, AFI may be useful in identifying blood pressure-related abnormalities, which represent an atherosclerotic risk in older Japanese women. ©2009, Editrice Kurtis.
  • Yoshiharu Kinugasa, Masahiko Kato, Shinobu Sugihara, Masayuki Hirai, Kazuhiko Kotani, Katsunori Ishida, Kiyotaka Yanagihara, Yosuke Kato, Kazuhide Ogino, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
    Circulation Journal 73(12) 2276-2281 2009年  査読有り
    Background: Risk stratification for elderly patients with acute decompensated heart failure (ADHF) may help clinicians to select the appropriate therapy and raise the quality of care. Methods and Results: The present study enrolled 349 patients aged over 65 years who were hospitalized with ADHF from January 2004 to October 2008. Five independent prognostic factors were identified by multivariate logistic regression analysis, and each factor was assigned a number of points proportional to its regression coefficient: prior heart failure hospitalization (2 points), sodium ≤138 mmol/L (2 points), BUN ≥35 mg/dl (2 points), albumin ≤3.2 g/dl (3 points), and BNP ≥980 pg/ml (2 points) in particular, hypoalbuminemia was identified as the strongest prognostic factor. The patients were stratified into 3 groups: low risk (0-4 points), moderate risk (5-7 points), and high risk (8-11 points). The respective in-hospital mortality rates were 1.6%, 15.8%, and 42.1% (P&lt 0.05). Conclusions: In addition to known prognostic factors, hypoalbuminemia may provide important information for elderly patients with ADHF. A simple risk score may help to stratify the risk of in-hospital mortality and contribute to better clinical management of these elderly patients.
  • Noriko Satoh, Akira Shimatsu, Kazuhiko Kotani, Akihiro Himeno, Takafumi Majima, Kazunori Yamada, Takayoshi Suganami, Yoshihiro Ogawa
    Hypertension Research 32(11) 1004-1008 2009年  査読有り
    A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, reduces the incidence of cardiovascular diseases. However, the detailed mechanism underlying the anti-atherogenic effect of EPA is still poorly understood. In this study, we examined the effect of EPA on cardio-ankle vascular index (CAVI), a new index of arterial stiffness that is less influenced by blood pressure (BP), as well as on serum amyloid A-low-density lipoprotein (SAA-LDL), an oxidized LDL (oxLDL), in the metabolic syndrome. Ninety-two obese Japanese subjects with metabolic syndromes were randomly divided into two groups (n=46): the EPA-treated group (1.8 g administered daily for 3 months) and the control group. Measurements were taken to assess the changes in glucose-lipid metabolism, SAA-LDL, C-reactive protein (CRP), leptin, adiponectin and pulse wave velocity (PWV), and CAVI. EPA treatment significantly reduced the levels of immunoreactive insulin, triglycerides, SAA-LDL, CRP, PWV and CAVI and increased the levels of adiponectin relative to the control group for 3 months (P&lt 0.05). Stepwise multivariate linear regression analysis revealed that the only significant determinant for a decrease in CAVI by EPA is a reduction in SAA-LDL (P&lt 0.05). Moreover, the EPA-induced reduction of SAA-LDL was only significantly correlated with a decrease in total cholesterol and an increase in adiponectin (P&lt 0.05). This study is the first demonstration that EPA improves arterial stiffness and is less influenced by BP, possibly through the suppression of SAA-LDL, thereby leading to a reduction in the frequency of cardiovascular disease development in metabolic syndrome.
  • Mami Fujibayashi, Taku Hamada, Tamaki Matsumoto, Natsuki Kiyohara, Seitaro Tanaka, Kazuhiko Kotani, Kahori Egawa, Yoshinori Kitagawa, Yoshinobu Kiso, Naoki Sakane, Toshio Moritani
    American Journal of Human Biology 21(6) 828-835 2009年  査読有り
    The present study is designed to investigate how and to what extent sympathovagal behavior in a balanced low-calorie diet relates to favorable changes of body mass, waist circumference, and/or metabolic risk factors. The study involved 28 mildly obese women without clinical complications, who underwent an 8-week calorie restriction program using a 1,200-kcal daily diet with an adequate nutrient content including two regular meals, and one formula meal replacement. All subjects were examined before and after the dietary intervention. We measured anthropometric parameters, blood pressure, and biochemical blood profiles for lipid metabolism. Autonomic nervous system activity was evaluated by heart rate variability power spectral analysis. The dietary intervention induced moderate, but significant reduction of waist circumference (25.3% 6 0.8%), body fat percentage (25.8% 6 0.8%), and body mass (26.6% 6 0.5%). Linear regression analysis showed that Δvery low frequency (VLF) power reflecting energy metabolic-and thermoregulatory sympathetic function significantly correlated to Δwaist circumference (r = 20.53, P &lt 0.01), Δbody fat percentage (r = -0.39, P &lt 0.05), Δbody mass (r = -0.43, P &lt 0.05), δHDL-cholesterol/total cholesterol ratio (HDL-C/TC) (r = 0.62, P &lt 0.001), and Δnonesterified fatty acids (NEFA) (r = 0.56, P &lt 0.01). A stepwise multiple regression analysis additionally revealed that Δwaist circumference (P = 0.024), ΔHDL-C/TC (P = 0.013), and ΔNEFA (P = 0.016) were significant and independent factors, which contributing to the variance in ΔVLF power (r2 = 0.61). Although causes and consequences of obesity continue to elude researchers, the present study indicates that thermoregulatory sympathetic activity relates to moderate waist-circumference reduction together with favorable changes of blood lipid profiles after short-term dietary modification in mildly obese women. © 2009 Wiley-Liss, Inc.
  • Noriko Satoh, Kazuhiko Kotani, Hiromichi Wada, Akihiro Himeno, Sayaka Shimada, Yousuke Sasaki, Kazunori Yamada, Akira Shimatsu, Koji Hasegawa
    Endocrine Journal 56(7) 915-918 2009年  査読有り
    Little information on the relationship between blood theology and atherosclerosis indicators in obese patients is available. We examined blood rheology as assessed by the blood passage time (BPT) with the microchannel method in 109 obese patients. BPT was correlated well with the extent of each metabolic syndrome component. A multivariate regression analysis revealed that the independent contributors to BPT were pulse-wave velocity, an index of arterial stiffness, body mass index and red blood cell. Furthermore, weight reduction intervention significantly decreased BPT. Assessment of rheology may be associated with pulse-wave velocity, and useful to manage obese patients.
  • Shuumarjav Uurtuya, Kazuhiko Kotani, Harumi Koibuchi, Nobuyuki Taniguchi, Toshiyuki Yamada
    Journal of Atherosclerosis and Thrombosis 16(3) 299-300 2009年  査読有り責任著者
  • Shinji Fujiwara, Kazuhiko Kotani, Yoshiko Sano, Yukiyo Matsuoka, Kokoro Tsuzaki, Masayuki Domichi, Eiji Kajii, Naoki Sakane
    Journal of Atherosclerosis and Thrombosis 16(3) 188-193 2009年  査読有り
    Aim: Lipoprotein lipase (LPL) plays an important role in lipid metabolism. There is an association between the common S447X polymorphism in the LPL gene and high-density lipoprotein cholesterol (HDL-C) levels, and some association between circulating HDL-C and adiponectin levels has been suggested however, it is not known whether there is any association between the S447X polymorphism and adiponectin levels. The aim of this study was to investigate whether the LPL S447X polymorphism was associated with adiponectin in the general population. Methods: LPL S447X was analyzed in 277 community-dwelling subjects (123 men and 154 women, mean age 65±13 years) in the Mima study. Whole samples were genotyped using a fluorescent allele-specific DNA primer assay system. The allele frequencies and any associations with serum lipid and adiponectin levels were investigated. Results: The allele frequencies were S=0.875 and X=0.125 for the LPL S447X polymorphism. The carriers of the X allele had significantly higher levels of adiponectin and HDL-C than non-carriers. The presence of the X allele was significantly associated with higher adiponectin levels, independent of age, sex, body mass index, smoking and HDL-C in multiple regression analyses. Conclusion: The LPL S447X polymorphism might therefore be significantly associated with higher adiponectin levels, independent of HDL-C.
  • Shuumarjav Uurtuya, Kazuhiko Kotani, Nobuyuki Taniguchi, Hiroaki Matsunaga, Hiroshi Kanai, Hideyuki Hasegawa, Kazuomi Kario, Shun Ishibashi, Kouichi Itoh
    Journal of Medical Ultrasonics 36(3) 129-135 2009年  査読有り責任著者
    Purpose: A new method has been developed for evaluating arterial stiffness using transcutaneous and high-frequency ultrasound. There may be a difference in the clinical significance of peripheral arteries, such as the radial artery (a muscular property), and other medium/large-sized arteries (an elastic property). The aim of this study was to determine the relationship between upper limb peripheral arterial stiffness (ULPAS) using the new method for the radial artery and atherosclerotic parameters in comparison with carotid intima-media thickness (IMT) and cardio-ankle vascular index (CAVI) in a healthy population and a diseased population with hypertension (HT) and diabetes mellitus (DM). Methods: Forty-four apparently healthy individuals (mean age = 26.3 years, men/women = 14/30), 45 patients with drug-treated HT (mean age = 55.3 years, men/women = 17/28), and 37 patients with drug-treated DM (mean age = 55.2 years, men/women = 21/16) were investigated. Body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), CAVI, IMT, ultrasonographically measured ULPAS, blood lipid/glucose-related parameters, and C-reactive protein (CRP) were all determined. Results: Among the healthy subjects, ULPAS showed a significantly positive correlation with SBP and CRP. ULPAS showed a different correlation pattern with atherosclerotic parameters from that of IMT and CAVI. The HT subjects had significantly higher ULPAS levels than those with DM. In this diseased population, ULPAS showed a significant positive correlation with SBP and DBP, as well as a significant negative correlation with glucose. Conclusion: These results suggest that ULPAS may provide new information in association with some atherosclerotic conditions as a unique index different from IMT and CAVI. © 2009 The Japan Society of Ultrasonics in Medicine.
  • Shuumarjav Uurtuya, Nobuyuki Taniguchi, Kazuhiko Kotani, Toshiyuki Yamada, Mikihiko Kawano, Nyamdavaa Khurelbaatar, Kouichi Itoh, Tserenkhuu Lkhagvasuren
    Hypertension Research 32(2) 140-144 2009年  査読有り
    Mongolian people have higher mortality and morbidity rates due to cardiovascular disease (CVD) than Japanese people. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are both atherosclerosis-related indexes. Presently, there is no comparative information on CAVI and ABI among young subjects between Mongolian and Japanese people. A total of one hundred Mongolian (men: 39%, mean age: 20.9±2.2 years) and 115 Japanese volunteers (men: 39%, mean age: 22.0±1.8 years) were recruited from among university students. The body mass index (BMI), heart rate (HR), blood pressure (BP), CAVI, ABI, carotid intima-media thickness, blood total cholesterol (TC), glucose and C reactive protein levels were measured. The levels of BMI, HR and diastolic BP were significantly higher, and TC and glucose were significantly lower in the Mongolian subjects than in the Japanese subjects. The CAVI values (median (interquartile range): 6.5 (5.8-7.0) vs. 5.6 (5.2-6.0)) and ABI (1.11 (1.05-1.17) vs. 1.09 (1.05-1.15)) were significantly higher in the Mongolian subjects than in the Japanese subjects. The patterns of correlation between CAVI, ABI and other atherosclerotic parameters were different: in age-, gender- and BMI-adjustment correlation tests for CAVI and ABI, HR (r=-0.25 for CAVI and ABI) showed a correlation in the Mongolian subjects, and for ABI systolic BP (r=-0.28) showed a correlation in the Japanese subjects. These results suggest that Mongolian subjects may be at higher risk of CVD, even among younger individuals, than Japanese subjects.
  • K. Kotani, S. Adachi, K. Tsuzaki, N. Sakane
    Age and Ageing 38(1) 123-126 2008年11月13日  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Hisashi Shimohiro, Seiji Adachi, Naoki Sakane
    Gerontology 54(6) 361-364 2008年11月  査読有り筆頭著者
    Background: Lipoprotein(a) [Lp(a)] or metabolic syndrome (MS) is individually considered an atherosclerotic factor. Serum Lp(a) may reportedly show the additive effects on atherosclerosis under certain particular pathologies. We do not know the association between serum Lp(a) and carotid artery intima-media thickness (CIMT) with relation to MS in older people. Objective: The present study aims at investigating the relationship between Lp(a) and CIMT levels in relation to MS among older subjects. Methods: We studied 182 Japanese subjects of ≥60 years (mean 72.5 years), free of cardiovascular/cerebrovascular disease. MS was based on the NCEP-ATPIII criteria with a minor modification for Japanese. The CIMT was ultrasonographically measured. Results: The CIMT levels were significantly greater in the MS group (n = 60, 1.03 ± 0.22 mm) than the non-MS group (n = 122, 0.96 ± 0.22 mm). Multivariate analysis, using Lp(a) levels or the product term for interaction between Lp(a) and MS, showed that age significantly and independently correlated to CIMT, along with male gender. Discussion: Even when Lp(a) and MS were simultaneously considered, age was the best determinant of CIMT in this population. The mechanism of our results including weak additive effects of Lp(a) and MS among older subjects may be partly throughout aging. Copyright © 2008 S. Karger AG.
  • Kazuhiko Kotani, Seiji Adachi, Yoneatsu Osaki, Youichi Kurozawa, Shigeru Araga
    Clinical Cardiology 31(10) 488-491 2008年10月  査読有り筆頭著者
    BACKGROUND: Hemorheology plays an important role in the development of cardiovascular disease. The Micro Channel array Flow Analyzer (MC-FAN) (Hitachi Haramachi Electronics Co., Ltd., Bentencho, Japan) is currently considered a useful new device to analyze hemorheology. However, the relationships between various lifestyle habits and hemorheology, especially using MC-FAN, have still not been thoroughly investigated. HYPOTHESIS: The study was undertaken to determine whether there could be some correlations of lifestyle factors to hemorheology by MC-FAN. METHODS: A total of 250 asymptomatic Japanese subjects (male:female = 100:150; mean age = 49.7 y) without any medication were enrolled in the present study. Hemorheology was assessed by the whole blood passage time (WBPT) and was corrected by the saline passage time using MC-FAN. Subjects' lifestyle factors, such as smoking habits, alcohol habits, and physical activity, were self-reported. RESULTS: Partial correlation analysis for WBPT, after controlling for age, gender, hematocrit, white blood cell count, body mass index, blood pressure, blood biochemical measures, and all lifestyle habits, revealed a significant and inverse correlation between alcohol habits of 1-3 go (amount of alcohol intake) and WBPT (r = - 0.191, p = 0.003), in addition to a significant positive correlation between serum low-density lipoprotein (LDL) cholesterol and WBPT. CONCLUSIONS: These data suggest that alcohol habits may beneficially affect hemorheology by MC-FAN, expanding the protective effect of light-to-moderate alcohol consumption against cardiovascular disease.
  • Kazuhiko Kotani, Kokoro Tsuzaki, Yoshiko Sano, Mizuho Maekawa, Shinji Fujiwara, Taku Hamada, Naoki Sakane
    Clinical Chemistry and Laboratory Medicine 46(10) 1434-1437 2008年10月1日  査読有り筆頭著者責任著者
    Background: Usual coffee consumption may decrease insulin resistance and type 2 diabetes incidence, and reduce cardiovascular disease risk. As a mechanism, coffee-induced lower levels of C-reactive protein (CRP), a marker for the development of these diseases, can be considered. The associations between coffee consumption and CRP should be established by studies on various populations, yet studies in Japanese people, who do not necessarily consume as much coffee daily, are limited. Methods: In total, 459 community-living Japanese women, aged 23-83 years, were investigated. Clinical data including age, body mass index, blood pressure, HbA1c, serum high sensitive CRP (hsCRP) and lifestyle habits, such as coffee consumption, were included in the analyses. All analyses were performed in two groups of the population, i.e., age &lt 60 and ≥60 years. Results: Significantly lower levels of hsCRP were observed in the group of ≥1 cup/day than in that of &lt 1 cup/day in the respective groups of &lt 60 years (p=0.001) and ≥60 years (p&lt 0.0001). In multiple regression analysis, coffee consumption was significantly, independently and inversely correlated to log-hsCRP in the respective groups of &lt 60 years (p=0.017) and ≥60 years (p&lt 0.0001). Conclusions: It was noteworthy that the benefits of coffee consumption, even if ≥1 cup/day, on serum hsCRP levels were confirmed in Japanese women, following similarly to other ethnic data. © 2008 by Walter de Gruyter.
  • Kazuhiko Kotani, Satoshi Kimura, Kokoro Tsuzaki, Naoki Sakane, Ichiro Komada, John Schulze, Alejandro Gugliucci
    Clinica Chimica Acta 395(1-2) 184-185 2008年9月  査読有り筆頭著者責任著者
  • Kenji Iijima, Hisashi Koike, Hiromi Ota, Mayumi Nakagawa, Ken-Ichi Nishikawa, Kazuhiko Kotani
    Rinsho byori. The Japanese journal of clinical pathology 56(8) 678-83 2008年8月  査読有り最終著者
    Nine clones of non-pathogenic streptococci were isolated from the pharynges of seven healthy subjects, and grown on sheep blood agar plates with a hemolysis or gamma hemolysis, then cultured in LB broth for 16 hrs. Purified streptolysin O (SLO) purchased from Sigma Chemical Co. (Sigma-SLO), SLO antigen as a latex agglutination reagent from A company (A-SLO) and supernatants from four culture media were electrophoresed on 12% SDS-polyacrylamide gel and transferred to PVDF membranes. Immunological analyses of antibodies against SLO in healthy sera and proteins in culture medium demonstrated that healthy sera contained an antibody recognizing Sigma-SLO, A-SLO and a protein of the same size as SLO (SLO-like protein) in culture medium. These findings suggest that healthy subjects develop an antibody directed against SLO-like protein produced by non-pathogenic streptococci, and that this antibody cross-reacts with Sigma-SLO and A-SLO. Using DNA from Streptococcus pyogenes and non-pathogenic streptococci, the SLO gene and SLO-like protein gene were analyzed by direct sequencing with oligonucleotide primers designed to cover no. 74 to approximately 1900 of the SLO gene. There were three different bases resulting in amino acid substitution between the SLO gene and SLO-like protein gene, namely 101Lys (AAA) of SLO to Asn (AAT), 175Met (ATG) to Arg (AGG) and 185Asp (GAT) to Asn (AAT). Remaining 560 residues of 563 amino acids constituting SLO-like protein were homologous to SLO. Non-pathogenic streptococci on the pharynges of healthy subjects produce an SLO-like protein composed of amino acids similar to those of SLO, which induces an antibody against this SLO-like protein in serum. It is likely that an antibody against SLO-like protein in healthy sera cross-reacts with SLO and causes a pseudo-positive reaction on ASO measurement by the latex agglutination method using SLO antigen.
  • Tomoyo Sawada, Takuji Kishimoto, Yoneatsu Osaki, Mikizoh Okamoto, Aya Tahara, Akihiko Kaetu, Yoichi Kurosawa, Kazuhiko Kotani
    Preventive Medicine 47(2) 167-171 2008年8月  査読有り最終著者
    Objective: To assess whether the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene possibly mediates the relation of blood pressure and serum cholesterol. Method: Regular health examination in 2003 of 1,694 Japanese workers from the Shimane Prefecture, Japan. Results: The frequencies of the Glu/Glu, Glu/Asp, and Asp/Asp genotypes were 85.9%, 13.4%, and 0.7%, respectively. After adjustment for age, sex, BMI, and lifestyle (drinking, smoking, exercise and stress), the odds ratio (OR) of hypertension associated with high (≥ 220 mg/dl or under treatment) total cholesterol was 2.08 (95% Confidence Interval (CI) 1.02-4.24) among carriers of the eNOS 298Asp allele versus 1.18 (95% CI 0.89-1.55, p for interaction = 0.50) among non-carriers. Similarly, the ORs of hypertension associated with counseling-need (120-139 mg/dl) and high (≥ 140 mg/dl) levels of LDL cholesterol among carriers of the eNOS 298Asp allele were significantly higher than those among non-carriers, at 2.65 (95% CI 1.16-6.01) versus 1.03 (95% CI 0.77-1.39, p for interaction = 0.01), and 2.80 (95% CI 1.33-5.89) versus 0.95 (95% CI 0.71-1.26, p for interaction = 0.04), respectively. Conclusion: These results indicate that the eNOS 298Asp allele, which is weakly associated with hypertension, may increase the risk of hypertension when associated with high serum lipid levels. © 2008 Elsevier Inc. All rights reserved.
  • Peter K. Kihato, Heizo Tokutaka, Masaaki Ohkita, Kikuo Fujimura, Kazuhiko Kotani, Yoichi Kurozawa, Yoshio Maniwa
    Neural Information Processing 274-284 2008年7月  査読有り
  • K. Kotani, S. Fujiwara, T. Hamada, K. Tsuzaki, N. Sakane
    Diabetes Care 31(5) e46 2008年5月1日  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Naoki Sakane, Youichi Kurozawa, Akihiko Kaetsu, Mikizo Okamoto, Yoneatsu Osaki, Takuji Kishimoto
    Annals of Clinical Biochemistry 45(3) 313-315 2008年5月  査読有り筆頭著者責任著者
    BACKGROUND: Polymorphism of Trp64Arg in the beta(3)-adrenergic receptor (beta(3)-AR) gene may play a critical role in lipid and lipoprotein metabolism by mediating lipolysis and thermogenesis. Since the frequency of Arg alleles of the beta(3)-AR gene is generally low among many populations, studies on the Arg/Arg genotype in relation to lipid and lipoprotein metabolism are required in countries such as Japan which has a relatively high frequency of the Arg allele. METHODS: We genotyped 275 clinically healthy Japanese (male/female, 134/141, mean 45.7 years) without medication for beta(3)-AR gene polymorphism by polymerase chain reaction-restriction fragment length polymorphism analysis, and investigated the effects of the gene polymorphism on clinical parameters including body mass index (BMI), blood pressure and serum lipid and lipoprotein concentrations. RESULTS: The genotype frequencies were: Trp/Trp, 68.0%; Try/Arg, 28.0% and Arg/Arg, 4.0%, with an allele frequency of 0.18 for Arg64. When subjects were divided into three groups according to the genotype, a significant increase of serum LDL-cholesterol (LDL-C) concentration in the Arg/Arg group (3.48 +/- 1.59 mmol/L) was observed when compared with those of the Trp/Trp and Arg/Trp groups (3.15 +/- 0.80, 3.25 +/- 0.92 mmol/L, respectively). Genotype differences did not show any significant effect on other parameters. Spearman's rank correlation demonstrated a significant relationship between LDL-C concentrations and the number of Arg alleles, age and BMI. Multiple regression analysis, using LDL-C concentration as a criterion variable and some factors including beta(3)-AR gene polymorphism as explanatory variables, revealed that the number of Arg alleles was a significant and independent factor for LDL-C concentrations, along with age and BMI. CONCLUSIONS: These findings suggested a role of the beta(3)-AR gene polymorphism in regulating lipid and lipoprotein metabolism, showing small but significant effects on elevated LDL-C values in subjects with Arg/Arg, but not Trp/Arg and Trp/Trp genotypes.
  • Kazuhiko Kotani, Kyoko Saiga, Naoki Sakane, Haosheng Mu, Youichi Kurozawa
    International Journal of Cardiology 125(3) 425-427 2008年4月25日  査読有り筆頭著者責任著者
    Sleeplessness can be linked to hypertension and its consequent complications such as cardiovascular disease. We investigated the cross-sectional relationship between blood pressure (BP) and self-reported sleep status among 227 healthy normotensive Japanese females (mean age: 47.0 years) in a clinical setting. Multiple logistic regression analysis for the highest quartile of diastolic BP (DBP) showed the body mass index (BMI) (odds ratio=1.26 [95% confidence interval=1.12-1.41]) and sleep status (sometimes lack: 2.19 [1.00-4.79], poor: 2.82 [1.17-6.80]) as significantly associated factors. The same analysis for systolic BP or pulse pressure showed that both age and BMI were significant factors and sleep status was not associated. A poorer sleep status may contribute to elevated DBP in healthy normotensive females.
  • Kazuhiko Kotani, Kyoko Saiga, Seiji Adachi, Naoki Sakane
    Archives of Medical Research 39(3) 360-361 2008年4月  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Hisashi Shimohiro, Seiji Adachi, Naoki Sakane
    The Tohoku Journal of Experimental Medicine 214(4) 321-325 2008年4月  査読有り筆頭著者責任著者
    Gamma-glutamyl transferase (GGT) is an enzyme present in serum and on most cell surfaces and serves as an oxidative stress marker. Although serum GGT is associated with hypertension development, little data are available on the associations between GGT and hypertension among populations with diabetes mellitus (DM). Our aim was to investigate the potential association between the changes in systolic or diastolic blood pressure (SBP/DBP) and the GGT level in type 2 DM subjects, in comparison with non-DM subjects. In 179 non-DM and 177 DM subjects, SBP/DBP, body mass index (BMI), fasting plasma glucose, serum asparate aminotransferase, alanine aminotransferase and GGT were measured at the baseline and after a 1-year period. Between these 2-measurement points, in non-DM subjects, SBP and DBP levels were significantly increased, while GGT tended to increase. In contrast, in DM subjects, the mean levels of SBP, DBP and GGT remained unchanged. Multivariate analysis revealed that in non-DM subjects the degree of increase in SBP was significantly and positively correlated to that of GGT (beta = 0.165), along with age and BMI. Likewise, the increase in DBP was correlated to that of GGT in non-DM subjects (beta = 0.170). In contrast, in DM subjects, the degree of increase in SBP was significantly correlated to that of only GGT (beta = 0.166). These results suggest that the presence of DM may attenuate the effects of GGT on DBP.
  • Taku Hamada, Kazuhiko Kotani, Akane Higashi, Junko Ikeda, Emi Tagaki, Aiko Igarashi, Chikanobu Matsubara, Toshihide Yoshida, Naoki Sakane
    The Tohoku Journal of Experimental Medicine 214(4) 365-370 2008年4月  査読有り
    A close relationship between coffee intake and certain metabolic disorders is known. Caffeine, one of coffee components, can increase energy expenditure (EE), but there are considerable individual differences in the caffeine effects on EE, and the causes have not been fully established in humans. The Arg allele in the beta(3)-adrenergic receptor gene (beta(3)-AR), a marker for obesity-related traits, may be a contributor to individual variations in EE. This study investigated the effect of the Arg allele of beta(3)-AR on caffeine-induced increases in EE. In 44 healthy young women (21 +/- 1 years), physical characteristics, blood pressure, biochemical profiles and dietary nutritional intake were measured. A caffeine-loading test was conducted at a dosage of 4 mg per body weight (kg). EE was measured using an indirect open-circuit calorimeter for a 10-min period before, and at 30 min and 60 min after the caffeine-loading test. The beta(3)-AR Trp64Arg polymorphism was detected with a PCR-restriction fragment length polymorphism method. The frequency of the Arg allele was 24%. The distribution of the Trp/Trp, Trp/Arg, and Arg/Arg genotypes was 58%, 36%, and 6%, respectively. At the baseline, subjects with the Arg/Arg genotype had a significantly lower EE level than those with the Trp/Trp or Trp/Arg genotype. After the caffeine-loading test, there were caffeine-induced increases in EE in all genotypes, but there were no differences in the levels of increase among the genotypes. These findings suggest that the genotypes of beta(3)-AR Trp64Arg polymorphism might be not associated with caffeine-induced increases in EE levels.
  • Kazuhiko Kotani, Hisashi Shimohiro, Seiji Adachi, Naoki Sakane
    Clinica Chimica Acta; international journal of clinical chemistry 389(1-2) 189-190 2008年3月  査読有り筆頭著者責任著者
  • Taku Hamada, Kazuhiko Kotani, Shinji Fujiwara, Yoshiko Sano, Masayuki Domichi, Kokoro Tsuzaki, Naoki Sakane
    Metabolism: clinical and experimental 57(3) 410-5 2008年3月  査読有り
    Uncoupling protein 3 (UCP3) is considered to be associated with obesity, given its function in the regulation of energy and lipid metabolism. An increased body mass index (BMI) and a decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors for cardiovascular disease. The purpose of this study was to investigate whether the UCP3 promoter -55 C/T single nucleotide polymorphism (UCP3 -55 C/T SNP) was associated with obesity according to the criteria for Japanese (BMI > or = 25 kg/m2), BMI, and serum HDL-C levels in the general Japanese population. The subjects, numbering 282 and aged 65 +/- 13 years (mean +/- SD), were recruited through an annual health checkup of residents of Mima city, Tokushima, in Japan. Body mass index, blood pressure, biochemical indexes including lipid, and lipoprotein profiles were measured. The UCP3 -55 C/T SNP was determined with a fluorescence-based allele-specific DNA primer assay system. The frequency of the -55 T allele was 30.0%. Subjects with the T/T genotype had significantly higher HDL-C levels than those with the C/C genotype or the C/T genotype. Furthermore, subjects with the T/T genotype had a significantly lower BMI than those with the C/C genotype. A multivariate analysis revealed that the -55 T allele was a significant independent variable contributing to the variance in HDL-C levels and BMI. The T/T genotype was associated with a lower prevalence of obesity than the C/C and C/T genotypes, with an odds ratio of 0.358 (95% confidence interval, 0.132-0.972; P = .037). In conclusion, the UCP3 -55 C/T SNP was associated with elevated HDL-C levels and a reduced BMI, independent of modifiable factors such as lifestyle. Furthermore, this polymorphism, when expressed in its homozygous form, reduced the prevalence of obesity in Japanese.
  • Taku Hamada, Kazuhiko Kotani, Shinji Fujiwara, Yoshiko Sano, Masayuki Domichi, Kokoro Tsuzaki, Kaoru Takahashi, Naoki Sakane
    Medical Science Monitor : international medical journal of experimental and clinical research 14(3) CR107-111 2008年3月  査読有り
    BACKGROUND: It has been reported that a common G-->A single nucleotide polymorphism (SNP) at the position -866 of the uncoupling protein-2 promoter (UCP2-866 G/A SNP) modulates UCP2 expression in adipose tissue and pancreatic beta-cell function, and lipid profiles. Reduced low density lipoprotein (LDL) particle size is a significant predictor of the development for coronary artery disease. The purpose of this study was to investigate whether the UCP2-866 G/A SNP was associated with serum LDL particle characteristics in a general Japanese population. MATERIAL/METHODS: In 279 subjects (age 65+/-13 years), body mass index (BMI), percent body fat, blood pressure, and blood biochemical profiles were measured. The UCP2-866 G/A SNP was determined with a fluorescence-based allele-specific DNA primer assay system. LDL particle characteristics were analyzed by high-resolution polyacrylamide gel electrophoresis. RESULTS: The frequency of the -866 A allele was 47.8%. There was no difference in triglyceride, total cholesterol, LDL-cholesterol, HDL-cholesterol, and small dense LDL levels between genotypes. However, subjects with the -866 A/A genotype had significantly lower mean LDL particle size levels (263.5+/-4.9 angstroms) than those with the -866 G/G genotype (264.6+/-4.9 angstroms, P=0.034). Multiple regression analysis revealed that the -866 A/A genotype was a significant variable contributing to the variance in the reduced LDL particle size levels (P=0.012). CONCLUSIONS: The -866 A/A genotype may contribute to reduced LDL particle size levels, a significant risk factor for the development of coronary artery disease.
  • Naoki Sakane, Taku Hamada, Kazuhiko Kotani
    Obesity research & clinical practice 2(1) 69-70 2008年3月  査読有り
  • Kazuhiko Kotani, Hisashi Shimohiro, Naoki Sakane
    Stroke 39(2) e32-33 2008年2月  査読有り筆頭著者
  • Haosheng Mu, Youichi Kurozawa, Kazuhiko Kotani, Guobin Liu, Pulin Liu, Atsushi Tsunekawa, Shunichiro Nishino, Takehiko Y. Ito
    Journal of Environmental Health 70(6) 38-43 2008年1月  査読有り
    This article elucidates the health-related quality of life (HRQOL) the recognition of desertification among people living in the semi-arid Loess Plateau of China. HRQOL was assessed with a three-dimensional survey of general health perception, vitality, and general mental health based on a 36-item short-form health survey (SF-36). Scores for general health perception were approximately the same in the city and the village communities. Vitality and mental health scores were significantly lower for women in the village communities than for other groups. In the village communities, HRQOL was significantly and positively correlated with income. The inhabitants of the village communities were more satisfied with their life situation than those in the city, in spite of the economic gap between them. Levels of recognition of desertification were lower in the village communities than in the city.
  • Kazuhiko Kotani, Naoki Sakane, Kokoro Tsuzaki, Yukiyo Matsuoka, Yoshiko Sano, Taku Hamada, Kazunori Yamada
    Scandinavian Journal of Clinical and Laboratory Investigation 68(7) 516-518 2008年1月  筆頭著者責任著者
  • Kazuhiko Kotani, Naoki Sakane, Kyoko Saiga, Seiji Adachi, Hisashi Shimohiro, Haosheng Mu, Youichi Kurozawa
    Archives of Medical Research 39(1) 142-146 2008年1月  査読有り筆頭著者責任著者
    BACKGROUND: A-3826G polymorphism within the promoter region of the uncoupling protein-1 (UCP-1) gene is possibly involved in the pathophysiology of obesity and metabolic disorders. However, the effects of UCP-1 A-3826G polymorphism on high-density lipoprotein cholesterol (HDL-C), a major contributor to atherosclerotic disease, still have not been established. METHODS: A total of 298 healthy Japanese subjects (144 males and 154 females, mean age: 45.2 years) with a body mass index (BMI) of 20.0-30.0 kg/m(2), regular lifestyles, and receiving no medication were enrolled in the cross-sectional study to estimate the relationship of serum HDL-C levels with UCP-1 A-3826G polymorphism by genomic PCR and Bcl1-restriction fragment length polymorphism analysis. We used 1.04 mmol/L of HDL-C in Japanese males and 1.29 mmol/L in Japanese females as cut-off values of low HDL-cholesterolemia. RESULTS: The genotype and allele frequencies of UCP-1 A-3826G polymorphism were similar to those previously reported in the Japanese population. In males, HDL-C levels of the GG genotype (1.75+/-0.49 mmol/L) were significantly higher than those found in the AA genotype (1.45+/-0.34 mmol/L, p=0.015). In females, the occurrence rate of low HDL-cholesterolemia was significantly different by genotype: a low prevalence in the GG genotype (15.4% in the AA, 4.8% in the AG, 15.4% in the GG genotype, p=0.022). Logistic regression analysis was used to identify risk factors for low HDL-cholesterolemia, with adjustments for age, gender, smoking, alcohol intake, BMI, hypertriglyceridemia, and genotype. The GG genotype was detected as being a significant associated factor (odds ratio =0.11 [95% confidence interval =0.01-0.90], p=0.01), in addition to BMI and the presence of hypertriglyceridemia. CONCLUSIONS: These results suggest that the GG genotype may be an independent protective factor associated with low HDL-cholesterolemia in this population, although the role of the UCP-1 A-3826G polymorphism in HDL-C is complex and remains controversial. This hypothesis needs further investigation.
  • Kazuhiko Kotani, Hisashi Shimohiro, Seiji Adachi, Naoki Sakane
    Clinical Chemistry and Laboratory Medicine 46(4) 541-544 2008年  査読有り筆頭著者責任著者
    BACKGROUND: Serum non-high-density lipoprotein cholesterol (HDL-C), an easily identifiable atherogenic index, has attracted attention within a clinical meaning different from that of other lipid indexes. The link between body weight gain and the occurrence of cardiovascular diseases may be mediated through non-HDL-C. However, there have been few reports examining the independent associations between weight gain and non-HDL-C, over a period of at least 1 year, especially in females. METHODS: We examined data on 200 asymptomatic Japanese females (mean 49.1 years) with an involuntary weight gain of at least > or = 0.1 kg/m2 as a body mass index (BMI) 1 year after a baseline check-up. At baseline and after the 1-year period, we measured BMI, blood pressure (BP) and blood metabolic variables, including non-HDL-C. RESULTS: The mean BMI levels rose from 22.9 to 23.5 kg/m2 during this period. Non-HDL-C levels had a significant increase (from 3.87 to 3.93 mmol/L), and a partial correlation test, adjusted for age and all measured metabolic variables, revealed that BMI change was significantly and independently correlated to non-HDL-C levels (r=0.25, p<0.0001), along with systolic BP. The subgroup with an age of <50 years had a clear correlation between BMI change and non-HDL-C levels (r=0.34, p=0.001), contrary to those of > or = 50 years. CONCLUSIONS: A short-term involuntary weight gain was significantly and independently correlated to an increase in non-HDL-C levels among asymptomatic Japanese females, particularly in relatively young subjects. In achieving a more favorable lipid profile of non-HDL-C, even a modest weight gain may need attention.
  • Kazuhiko Kotani, Hisashi Shimohiro, Narumi Nagai, Mizuho Maekawa, Naoki Sakane
    Gerontology 54(5) 281-282 2008年  査読有り筆頭著者責任著者
  • Noriko Satoh, Akira Shimatsu, Yasuhisa Kato, Rika Araki, Kazunori Koyama, Taiichiro Okajima, Makito Tanabe, Mariko Ooishi, Kazuhiko Kotani, Yoshihiro Ogawa
    Hypertension Research 31(10) 1921-1930 2008年  査読有り
    Aortic stiffness is predictive of cardiovascular diseases (CVD) and mortality in lifestyle-related diseases. The cardio-ankle vascular index (CAVI), a new index of arterial stiffness, was recently developed by measuring of pulse wave velocity (PWV) and blood pressure (BP). CAVI is adjusted for BP based on stiffness parameter β and is less influenced by BP, suggesting its superiority over brachial-ankle PWV (baPWV). However, there are currently no reports on the usefulness of CAVI as an atherogenic index in obesity and metabolic syndrome (MS). Among the 325 obese Japanese outpatients enrolled in the multi-centered Japan Obesity and Metabolic Syndrome Study, 216 patients (67%) met the criteria of MS according to the modified National Cholesterol Education Program-Adult Treatment Panel III. CAVI values were significantly higher in MS than in non-MS patients, whereas there was no significant difference in body mass index, total cholesterol, and low-density lipoprotein-cholesterol between both groups. CAVI values were weakly correlated with BP but closely correlated with the severity of MS and MS-related parameters such as hypoadiponectinemia, relative to baPWV. Furthermore, weight-reduction therapy through diet and exercise over a 3-month period significantly decreased CAVI values in parallel with increasing adiponectin. This study demonstrates for the first time that CAVI is a good indicator of arterial stiffness. It is closely correlated with the severity of MS and CVD risks in obesity and independent of BP, and is thus superior to baPWV. Therefore, the determination of arterial stiffness by CAVI may be useful for evaluating and managing the CVD risks of MS patients.
  • Naoki Sakane, Shinji Fujiwara, Yoshiko Sano, Masayuki Domichi, Kokoro Tsuzaki, Yukiyo Matsuoka, Taku Hamada, Kyoko Saiga, Kazuhiko Kotani
    Endocrine Journal 55(3) 485-488 2008年  査読有り
    Oxidative stress and inflammation are known to play roles in the pathogenesis of vascular events. The aim of this study was to investigate the relationship between oxidative stress, inflammation, and atherosclerosis in the general population, A population-based, cross-sectional study was made of 282 people (126 men and 156 women, mean age 65 ± 13, mean BMI 25.4 ± 2.7 kg/m2) recruited from the Mima study in Tokushima Prefecture. Risk factors included age, sex, body mass index (BMI), cigarette smoking, systolic and diastolic pressure, fasting blood glucose, serum lipids, and high-sensitive C-reactive protein (hs-CRP). Oxidative stress in blood samples was measured by the diacron reactive oxygen metabolites (ROMs) test. The degree of sclerotic change was determined from fundus photographs according to Scheie's classification. After adjustment for age and sex, ROM levels positively correlated with hs-CRP levels, but not with ghrelin, leptin and adiponectin levels. Furthermore, ROM and hs-CRP levels positively and individually correlated with the grade of sclerotic change in the fundus oculi independent of age in a multiple regression analysis. These results suggest that oxidative stress and chronic inflammation promote atherosclerosis in the retinal arteries in the general population.
  • Naoki Sakane, Kazuhiko Kotani, Chizuko Hioki, Toshihide Yoshida, Teruo Kawada
    Endocrine Journal 54(5) 771-775 2007年12月  査読有り
    To examine whether benidipine hydrochloride, one of the calcium channel blockers, up-regulate uncoupling protein 3 (UCP3) expression in two skeletal muscles (gastrocnemius and soleus) in rats. Wistar rats were treated orally with benidipine hydrochloride at 4 mg/kg for 7 days. Blood pressure was measured after 4 days. At the end of experiments, the rats were weighed, and brown adipose tissue (BAT) and skeletal muscles (gastrocnemius and soleus muscles) were removed. The mRNA levels of uncoupling protein 1 (UCP1) and UCP3 were measured using the real-time quantitative reverse transcription-polymerase chain reaction method. Benidipine reduced body weight and also had a hypotensive effect. In rats treated with benidipine, UCP1 mRNA levels were significantly increased 1.4-fold in BAT, and UCP3 mRNA levels in BAT and gastrocnemius muscle were significantly increased 1.7 and 3.0-fold, respectively, compared with the control rats. There was no difference in UCP3 mRNA levels in soleus muscle between the two groups. We concluded that benidipine up-regulates not only UCP1 gene expression in BAT but also UCP3 gene expression in BAT and gastrocnemius muscle, which may contribute to thermogenesis in rats.
  • Kokoro Tsuzaki, Kazuhiko Kotani, Shinji Fujiwara, Yoshiko Sano, Yukiyo Matsuoka, Masayuki Domichi, Taku Hamada, Akira Shimatsu, Naoki Sakane
    Metabolism: clinical and experimental 56(12) 1689-1693 2007年12月  査読有り
    The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor (beta(3)-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the beta(3)-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose x fasting insulin/405) were determined. The polymorphism of the beta(3)-AR gene was assessed by polymerase chain reaction-restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the beta(3)-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the beta(3)-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the beta(3)-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.
  • Naoki Sakane, Taku Hamada, Kazuhiko Kotani, Akane Higasi, Chikanobu Matsubara
    Obesity research & clinical practice 1(4) 223-9 2007年12月  査読有り
  • Kazuhiko Kotani, Hisashi Shimohiro, Naoki Sakane
    The Tohoku Journal of Experimental Medicine 213(4) 369-372 2007年12月  査読有り筆頭著者責任著者
    Internal stress can modify values in blood examinations such as glucose. Mood change releases us from the stress state, and the mood change tendency (MCT) may show individual differences. However, little is known about whether individual mood change tendencies in daily life affect fasting plasma glucose (FPG) levels. We investigated the effects of clinical characteristics including age, body mass index (BMI), smoking, alcohol habits and self-reported MCT (an answer to the inquiry on their daily MCT: good, average, or poor) on FPG values among 272 Japanese females (mean age 48.4 +/- 9.3 years). Subjects with normal to impaired fasting glucose levels (less than 7.0 mmol/L) were included in this study. The mean FPG levels in subjects with good, average and poor MCT were 5.32 +/- 0.48, 5.36 +/- 0.50 and 5.58 +/- 0.69 mmol/L, respectively. A significant difference was noted between subjects with good and poor MCT (p = 0.02). There was no significant difference in BMI levels among MCT-based groups. Pearson's rank correlation and multiple regression analysis, using FPG levels and other variables, demonstrated a significant relationship between FPG levels and MCT (p < or =0.01), along with age and BMI. These results suggest slight but significant effects of individual MCT on FPG, and that a consideration of MCT may occasionally be needed in the interpretation and management of FPG levels in the Japanese female population.

MISC

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共同研究・競争的資金等の研究課題

 38