Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction.
Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction.
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DOI：
10.1007/s00125-009-1524-3
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发表时间：
2009-12
期刊：
影响因子：
8.2
通讯作者：
Snieder, H.
中科院分区：
文献类型：
--
作者：
Wang, X.;Ding, X.;Su, S.;Spector, T. D.;Mangino, M.;Iliadou, A.;Snieder, H.
候选基因研究的证据表明，肥胖可能会改变2型糖尿病和血脂异常的遗传易感性。在总体水平上，基因与肥胖的相互作用预计会导致不同肥胖水平的遗传力估计不同。然而，这一假设从未得到检验。目前的研究包括2180对英国女性双胞胎。体重指数被用作一般肥胖症的指标。观察指标为胰岛素敏感性(用定量胰岛素敏感性检查指数[QUICI]表示)和空腹血脂谱。结构方程模型被用来检验BMI是否与潜在的遗传和环境效应相互作用，以影响结果测量。遗传对三酰甘油的影响随着体重指数的增加而增加(p <； 0.001)，而对Quicki的独特环境影响随着体重指数的减少而减少(p <； 0.001)，导致在较高的体重指数水平下这两个指标的遗传力估计都较高。对正常体重的双胞胎和超重的双胞胎进行分层分析，进一步说明了这一点。在符合超重标准的双胞胎中，三酰甘油(p <； 0.001)的遗传率比符合正常体重的双胞胎高19个百分点，Quicki(p <； )的遗传率高31个百分点。BMI对总胆固醇和高密度脂蛋白-胆固醇的潜在遗传和环境因素没有调节作用。我们的结果表明，影响三酰甘油和胰岛素敏感性的基因的表达可能会随着肥胖状况的不同而变化。体重指数较高时，遗传因素对胰岛素敏感性和三酰甘油总变异的显著增加，可能被证明在寻找候选基因方面非常有价值。
Evidence from candidate gene studies suggests that obesity may modify genetic susceptibility to type 2 diabetes and dyslipidaemia. On an aggregate level, gene–obesity interactions are expected to result in different heritability estimates at different obesity levels. However, this hypothesis has never been tested. The present study included 2,180 British female twins. BMI was used as an index of general obesity. Outcome measures were insulin sensitivity (indexed by quantitative insulin-sensitivity check index [QUICKI]) and fasting plasma lipid profile. Structural equation modelling was used to test whether BMI interacted with latent genetic and environmental effects to impact on the outcome measures. Genetic influences on triacylglycerol increased with BMI (p < 0.001) whereas the unique environmental influence on QUICKI decreased with BMI (p < 0.001), resulting in a higher heritability estimate for both measures at higher BMI levels. This was further illustrated by stratified analysis in twin pairs concordant for normal weight and twin pairs concordant for overweight. Heritability was 19 percentage points higher for triacylglycerol (p < 0.001) and 31 percentage points higher for QUICKI (p < 0.01) among twins concordant for overweight than among twins concordant for normal weight. BMI had no moderator effect on the latent genetic and environmental factors for total cholesterol and HDL-cholesterol. Our results suggest that the expression of genes influencing triacylglycerol and insulin sensitivity can vary as a function of obesity status. The substantial increases in the genetic contribution to the total variance in insulin sensitivity and triacylglycerols at higher BMIs may prove extremely valuable in the search for candidate genes.
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影响因子：
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通讯作者：
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