载脂蛋白 A1/C3/A4/A5 基因簇上与血脂异常相关的遗传多态性影响的男性中心性肥胖。

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

机构信息

1] Research Center for Medical Laboratory Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan [2] Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Nutr Diabetes. 2013 Mar 4;3(3):e61. doi: 10.1038/nutd.2013.2.

DOI:10.1038/nutd.2013.2

PMID:23459084

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3608892/

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.

摘要

背景

中心性肥胖是一种日益流行的疾病，常与血脂异常同时发生。此外，在脂质代谢控制改变的人类研究和动物模型中，都观察到异位脂肪沉积增加。虽然 APOA1/C3/A4/A5 基因多态性与血脂异常有关，但它们对中心性肥胖的影响知之甚少。

方法

在开始减肥干预时和 6 个月后，从肥胖（体重指数（BMI）≥25kg/m²）和非肥胖健康（BMI＜25）的台湾患者中获取人体测量和代谢参数。分析 APOA1/C3/A4/A5 基因多态性的横断面和纵向效应。特别检查了性别贡献。

患者

共招募了 398 名参与者（肥胖组 n=262；非肥胖健康组 n=136），其中 130 名肥胖患者接受了减肥治疗。

结果

APOA5 rs662799 次要等位基因携带者在肥胖患者中存在不利的代谢特征，但在非肥胖个体中没有。进一步分析发现腰围-臀围比（WHR）存在性别-基因型相互作用，线性回归分析表明，在调整年龄、BMI 和血浆甘油三酯（TG）后，一个 rs662799 次要等位基因使肥胖男性的 WHR 增加 0.032 个单位（95%置信区间（CI）=0.014-0.050，P=0.001）。APOA5 rs662799 相关的 WHR 升高导致 rs662799 携带的肥胖男性中心性肥胖（WHR≥1.0）的频率增加，这是通过调整年龄、BMI 和血浆 TG 的二元逻辑回归分析得出的（比值比=6.52，95%CI=1.87-22.73，P=0.003）。相反，由于男性 rs662799 次要等位基因携带者的 WHR 显著降低，APOA5 rs662799 和中心性肥胖在减肥治疗 6 个月后不再相关（P=0.001）。同时，在肥胖的 rs662799 次要等位基因携带者中，基线时男性和女性的高甘油三酯血症更为普遍（男性，P=0.034，女性，P=0.007）。