The interaction of Apolipoprotein A5 gene promoter region T-1131C polymorphism (rs12286037) and lifestyle modification on plasma triglyceride levels in Japanese.

BACKGROUND/OBJECTIVE: Apolipoprotein A5 gene promoter region T-1131C polymorphism (APOA5 T-1131C) is known to be associated with elevated plasma TG levels, although little is known of the influence of the interaction between APOA5 T-1131C and lifestyle modification on TG levels. To investigate this matter, we studied APOA5 T-1131C and plasma TG levels of subjects participating in a three-month lifestyle modification program. SUBJECTS/METHODS: A three-month lifestyle modification program was conducted with 297 participants (Age: 57 ± 8 years) in Izumo City, Japan, from 2001-2007. Changes in energy balance (the difference between energy intake and energy expenditure) and BMI were used to evaluate the participants' responses to the lifestyle modification. RESULTS: Even after adjusting for confounding factors, plasma TG levels were significantly different at baseline among three genotype subgroups: TT, 126 ± 68 mg/dl; TC, 134 ± 74 mg/dl; and CC, 172 ± 101 mg/dl. Lifestyle modification resulted in significant reductions in plasma TG levels in the TT, TC, and CC genotype subgroups: -21.9 ± 61.0 mg/dl, -20.9 ± 51.0 mg/dl, and -42.6 ± 78.5 mg/dl, respectively, with no significant differences between them. In a stepwise regression analysis, age, APOA5 T-1131C, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and the 18:1/18:0 ratio showed independent association with plasma TG levels at baseline. In a general linear model analysis, APOA5 T-1131C C-allele carriers showed significantly greater TG reduction with decreased energy balance than wild type carriers after adjustment for age, gender, and baseline plasma TG levels. CONCLUSIONS: The genetic effects of APOA5 T-1131C independently affected plasma TG levels. However, lifestyle modification was effective in significantly reducing plasma TG levels despite the APOA5 T-1131C genotype background.

MC4R rs17782313 gene polymorphism was associated with glycated hemoglobin independently of its effect on BMI in Japanese: the Shimane COHRE study.

BACKGROUND: Type 2 diabetes (T2D) is among the leading public health problems in Japan, and glycated hemoglobin (HbA1c) can be used to screen the population for T2D. Gene polymorphisms, known to be associated with obesity, may predispose individuals to T2D. Rs17782313 the melanocortin 4 receptor (MC4R) has shown one of the strongest associations with body mass index (BMI). We conducted a study to investigate whether rs17782313 (TT versus TC + CC) was associated with HbA1c. METHOD: We conducted a cross-sectional study including 1142 Japanese adults (446 men: 64.9 ± 14.4 years and 696 women: 66.7 ± 12.3 years). MC4R rs17782313 was genotyped using fast real-time polymerase chain reaction. RESULTS: TC + CC genotype group showed significantly greater BMI (p = 0.039) and HbA1c (p = 0.001) than TT genotype group after adjustment for gender, age and, for HbA1c, BMI. Further analysis using linear regression analysis confirmed that the effect of MC4R rs17782313 on HbA1c (ß = 0.08; p = 0.003) was independent of the effect age, gender, BMI, low density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and of beta cell function. This significant independent association was similarly noticed in non-obese (ß = 2.82; p = 0.005) subgroups. CONCLUSION: MC4R rs17782313 was associated with obesity and could confer a certain susceptibility to T2D that could be independent of its pro-obesity effect.

Cannabinoid Receptor 1 (CNR1) 4895 C/T Genetic Polymorphism was Associated with Obesity in Japanese Men.

AIM: The aim of this study was to investigate the association of cannabinoid receptor 1 (CNR1) 4895 C/T gene polymorphism with obesity and obesity-related cardiovascular disease (CVD) risk factors in Japanese. METHOD: This study included 1,452 Japanese (678 men and 774 women, aged 25 to 74) from rural communities in Shimane Prefecture, Japan. RESULTS: The frequency of the C minor allele of CNR1 4895 C/T polymorphism was 47%. In men, the CC genotype carriers showed significantly greater body mass index (BMI) and waist circumference (WC) values than T allele carriers, even after adjusting for age and medications for hypertension, dyslipidemia and type 2 diabetes. The frequency of obesity (BMI ≥25 kg/m(2)) in CC genotype carriers was significantly greater than in T allele carriers (31.8% vs 21.5%), but the frequency of central obesity (WC ≥85 for men and WC ≥90 cm for women) was not significant by CNR1 4895 C/T genotype. CC genotype carriers of CNR1 4895 C/T showed, in logistic regression analysis, significantly greater odds for obesity than T allele carriers, even after adjustment for age and the above-mentioned medications. Systolic blood pressure (SBP) values were also significantly different between the CC genotype and T allele carriers after controlling for age, medications for hypertension, dyslipidemia, and type 2 diabetes, and BMI or WC. CONCLUSION: This study supports the association of CNR1 4895 C/T with interindividual differences in obesity in men.