Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
J Clin Endocrinol Metab. 2010 May;95(5):2418-25. doi: 10.1210/jc.2009-2077. Epub 2010 Mar 9.
Recent genome-wide association studies have identified multiple novel loci associated with obesity in Europeans. We hypothesized that these genetic variants may be associated with obesity and type 2 diabetes (T2D) in Chinese.
We examined 14 associated single-nucleotide polymorphisms at 12 loci (NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15) in 605 healthy adults, 1087 healthy adolescents and 6013 T2D patients from Hong Kong.
The European at-risk alleles at five loci including GNPDA2, BCDIN3D/FAIM2, SH2B1, FTO, and KCTD15 were significantly associated with increased body mass index (BMI), waist circumference (4.5 x 10(-8) < P < 0.024), and/or obesity risk (odds ratio 1.14-1.22, 2.0 x 10(-5) < P < 0.002) in our Chinese populations. The former four loci as well as LIN7C/BDNF were also modestly associated with T2D risk (odds ratio 1.09-1.22, 0.008 < P < 0.041), but the associations were lost after adjustment for BMI, suggesting their roles in T2D risk are mediated through modulation of adiposity. Joint effect analyses of the five adiposity loci revealed an increase of about 0.29 kg/m(2) in BMI with each additional copy of at-risk allele (P(trend) = 4.2 x 10(-12)).
Our findings support the important contribution of GNPDA2, BCDIN3D/FAIM2, SH2B1, FTO, and KCTD15 in the regulation of adiposity, which in turn affects T2D risk in Chinese.
最近的全基因组关联研究已经确定了多个与欧洲人肥胖相关的新基因位点。我们假设这些遗传变异可能与中国人的肥胖和 2 型糖尿病（T2D）有关。
我们在香港的 605 名健康成年人、1087 名健康青少年和 6013 名 T2D 患者中检查了 12 个基因座（NEGR1、SEC16B、TMEM18、ETV5/DGKG、GNPDA2、LIN7C/BDNF、MTCH2、BCDIN3D/FAIM2、SH2B1、FTO、MC4R 和 KCTD15）的 14 个相关单核苷酸多态性。
五个基因座（GNPDA2、BCDIN3D/FAIM2、SH2B1、FTO 和 KCTD15）的欧洲危险等位基因与体重指数（BMI）、腰围（4.5×10(-8) < P < 0.024）和/或肥胖风险（比值比 1.14-1.22，2.0×10(-5) < P < 0.002）显著相关在我们的中国人群中。前四个基因座以及 LIN7C/BDNF 也与 T2D 风险适度相关（比值比 1.09-1.22，0.008 < P < 0.041），但在调整 BMI 后这些关联就消失了，这表明它们在 T2D 风险中的作用是通过调节脂肪量来介导的。对五个肥胖基因座的联合效应分析显示，每增加一个危险等位基因，BMI 增加约 0.29kg/m(2)（P(trend) = 4.2×10(-12))。
我们的研究结果支持 GNPDA2、BCDIN3D/FAIM2、SH2B1、FTO 和 KCTD15 在调节脂肪量方面的重要作用，进而影响中国人的 T2D 风险。
