Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Obesity (Silver Spring). 2010 Feb;18(2):425-9. doi: 10.1038/oby.2009.254. Epub 2009 Aug 13.
Recent genome-wide association studies (GWAS) in Asian Indians reported strong associations of variants near melanocortin-4 receptor (MC4R) and MLX interacting protein-like (MLXIPL) genes with insulin resistance and several obesity-related quantitative traits (QTs). Here, we evaluated the association of two variants (rs12970134 and rs4450508) near MC4R and a nonsynonymous (Gln241His) variant (rs3812316) in MLXIPL gene with type 2 diabetes (T2D) and obesity-related QTs in our case-control cohort (n = 1,528; 745 T2D cases and 783 controls) from a Sikh population from North India. We have successfully replicated the association of MC4R (rs12970134) with BMI (P = 0.0005), total weight (WT) (P = 0.001), and waist circumference (WC) (P = 0.001). These associations remained significant after controlling for multiple testing by applying Bonferroni's correction. However, our data did not confirm the association of rs3812316 in the MLXIPL gene with triglyceride (TG) levels. These observations demonstrate that the genetic variation in MC4R locus can have a moderate contribution in the regional fat deposition and development of central obesity in Asian Indians.
最近的全基因组关联研究（GWAS）在亚洲印度人中报告了黑素皮质素-4 受体（MC4R）和 MLX 相互作用蛋白样（MLXIPL）基因附近的变异与胰岛素抵抗和几种肥胖相关的定量特征（QT）之间存在强烈关联。在这里，我们评估了 MC4R 附近的两个变异（rs12970134 和 rs4450508）和 MLXIPL 基因中的一个非同义（Gln241His）变异（rs3812316）与我们来自印度北部锡克教人群的病例对照队列（n = 1528；745 例 2 型糖尿病（T2D）病例和 783 例对照）中 2 型糖尿病（T2D）和肥胖相关 QT 的关联。我们成功复制了 MC4R（rs12970134）与 BMI（P = 0.0005）、总体重（WT）（P = 0.001）和腰围（WC）（P = 0.001）的关联。在应用 Bonferroni 校正进行多重检验控制后，这些关联仍然显著。然而，我们的数据并未证实 MLXIPL 基因中的 rs3812316 与甘油三酯（TG）水平之间的关联。这些观察结果表明，MC4R 基因座的遗传变异可以在亚洲印度人中对区域性脂肪沉积和中心性肥胖的发展产生中等贡献。
