Central obesity in males affected by a dyslipidemia-associated genetic polymorphism on APOA1/C3/A4/A5 gene cluster

Abstract

Background:Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known.Method:The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) ⩾25 kg m−2) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined.Patients:Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments.Results:APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender–genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014–0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR ⩾1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87–22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007).Conclusion:This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

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

“…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,…”

A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia

“…Not surprisingly, by virtue of the APOA1 protein function in cholesterol efflux, mutations in the encoding gene have recently been implicated in disorders of the lipoprotein metabolism, such as high-density lipoprotein deficiency type 1 (HDLD1) and type 2 (HDLD2) as well as metabolic syndrome (28)(29)(30). Thereby, the rs1558861 on the APOA1 conspicuously exhibited disease-causative characteristics.…”

Phosphorylation of glycogen synthase kinase-3β in metabolically abnormal obesity affects immune stimulation-induced cytokine production

“…Exclusion criteria included current smokers, alcohol consumers (more than two drinks per day), diagnosis of inflammatory disease or cancer, and use of hormone replacement therapy. 18 The study protocol was approved by the NCKUH Institutional Research Review Board.…”