The interaction ofApolipoprotein A5gene promoter region T-1131C polymorphism (rs12286037) and lifestyle modification on plasma triglyceride levels in Japanese

Abstract

BACKGROUND/OBJECTIVEApolipoprotein 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/METHODSA 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.RESULTSEven 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.CONCLUSIONSThe 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.

Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations

“…Gene-weight interactions have also been reported for individual SNPs, including those associated with APOA5 26,[32][33][34] , LPL 26,[35][36][37][38][39][40][41][42][43] , GCKR 26,44 , insulin receptor substrate-1 (IRS-1) 45,46 , methylenetetrahydrofolate reductase (MTHFR) 47,48 , proprotein convertase subtilisin/kexin type 9 (PCSK9) 48 , APOB 49 , APOE 50 , peroxisome proliferator-activated receptor γ 2 (PPARγ2) 51 , and patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) 52 .…”

“…Environmental factors that distinguish higher vs. lower triglycerides (e.g., obesity, physical inactivity, smoking, alcohol, high-carbohydrate diets, T2DM) are predicted to produce different genetic estimates under quantile-dependent expressivity. Traditionally, these differences have been attributed to gene-environment interactions, where: 1) the effect of the genotype on the phenotype differs by environment [26][27][28][29][30][31][32][33][34][35][36][37][41][42][43][45][46][47][48][49][50][51][52][53][54][55][58][59][60][61][62][63][65][66][67][74][75][76][77][78][79][80] , or equivalently: 2) the effect of the environment on the phenotype differs by genotype 36,[38][39][40]44,…”

Variants in <b><i>APOA5</i></b> and <b><i>ADIPOQ</i></b> Moderate Improvements in Metabolic Syndrome during a One-Year Lifestyle Intervention

“…Additionally, a 3-month intervention consisting of diet quality improvements and regular walking in individuals with hypertriglyceridemia showed greater improvements in major allele carriers for both APOA-V and triglyceride levels compared to minor allele carriers, despite a similar degree of compliance [32]. In contrast, the aforementioned genotype effect in response to a lifestyle intervention was not observed in a Japanese cohort [33]. Collectively, these studies suggest a potential moderating effect for rs662799 on blood triglyceride levels in response to longer-term lifestyle interventions.…”

The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women

“…This can be partly explained by the different lifestyles between Chinese men and women. It has been reported that the rs662799 polymorphism had interaction with lifestyles on the lipid levels in Asians [ 28 ]. The gender-specific effects of the rs662799 polymorphism on lipid levels were also reported in other populations.…”