小谷 和彦

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

BACKGROUND: Serum adiponectin concentration plays a role in the development of metabolic and atherosclerotic diseases. Although elucidating the determinants that affect circulating adiponectin concentrations including lifestyle factors are important, little is known about the relationships between lifestyle and adiponectin in the general Japanese female population. METHODS: A total of 311 Japanese females (mean age 54 years) with normal lifestyles and taking no medications were enrolled in a community-based cross-sectional study to investigate which lifestyle factors were associated with serum adiponectin concentrations. Adiponectin was measured with an enzyme-linked immunosorbent assay. The modified Breslow's index (a well-known comprehensive index) was used in assessing lifestyle factors. RESULTS: The group of moderate drinkers (consuming 1-3 go/day on average) had significantly higher serum adiponectin concentrations than that of nondrinkers (consuming <1 go/day) (15.0 +/- 7.2 vs. 12.0 +/- 6.5 microg/mL). Using a partial correlation analysis on serum adiponectin concentrations adjusted for age and all lifestyle factors, there were significant positive correlations with age (r = 0.197) and alcohol intake (r = 0.130) and a significant inverse correlation with body mass index (BMI) (r = -0.178). CONCLUSIONS: Among many lifestyle factors, in addition to maintaining decreased BMI levels, moderate alcohol intake habits may have a significant, independent, and positive effect on adiponectin concentrations in the general population of Japanese females, similar to that of Caucasian populations.

BACKGROUND: Protein 1 (P1)/Clara cell 16 kDa protein (CC16, previously named CC10), a potentially immunosuppressive protein secreted by non-ciliated cells of the tracheobronchial epithelium, has been found to be a new useful lung-specific biomarker in several pathological lung conditions. Particularly, urinary P1 (uP1) may reflect the altered lung functions in pneumoconiosis. METHODS: We investigated the relationship between uP1 values and lung functions in 31 non-smoking pneumoconiotic males (mean age 73 years) with a history of dust exposure work in shipbuilding. The protein was measured using an originally prepared enzyme-linked immunosorbent assay system. The forced expiratory volume in 1 s % (FEV(1.0)%) and % vital capacity (%VC) were tested with a spirometer. RESULTS: The mean values of uP1 were 4.62 +/- 4.82 (mean +/- standard deviation) ng/mol creatinine. A univariable correlation test showed a significant positive correlation between uP1 and %VC (r = 0.356, P = 0.049). Also, a multiple regression analysis, when adjusted for age, disease duration, FEV(1.0)% and %VC, showed a significant correlation of uP1 with %VC (beta = 0.467, P = 0.030). CONCLUSION: The results suggest that a decreased uP1, corroborated by a decreased %VC, may be the result of damage to secretory cells. Measurement of uP1 may become a possible index of fibrotic changes in pneumoconiosis.

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene has been reported to predict a lower risk for developing type 2 diabetes mellitus. However, its effect on the lipid profile has been disputable. Among low-density lipoproteins, small dense low-density lipoprotein (sdLDL) particles have been linked to a greater risk for coronary artery disease. The purpose of this study was to investigate the genetic effect of the Pro12Ala polymorphism in the PPARgamma2 gene on the presence of sdLDL in the general Japanese population. In 379 subjects (aged 54 +/- 13 years), body mass index, percentage of body fat, blood pressure, and biochemical profiles were measured. Pro12Ala polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The area of sdLDL subfractions (sdLDL4-7) was analyzed by high-resolution polyacrylamide gel electrophoresis. The frequency of the Ala12 allele in PPARgamma2 was 0.04. There was no difference in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels between genotypes. However, subjects with the X/Ala genotype (Pro/Ala + Ala/Ala) had significantly higher serum triglyceride levels (P = .001) and a larger area of sdLDL4-7 (P = .002) than those with the Pro/Pro genotype. Multiple regression analysis revealed that the Ala12 allele was a significant variable contributing to the variance in the increased area of sdLDL4-7 (P = .040). In conclusion, the Pro12Ala polymorphism in the PPARgamma2 gene was positively associated with an enlarged area of sdLDL4-7. This polymorphism may play a role in the genetic predisposition to increases in sdLDL4-7.