Departamento de Genética y Biología Molecular, Centro de Investigación yde Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
BMC Med Genet. 2013 Feb 1;14:21. doi: 10.1186/1471-2350-14-21.
Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children.
The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N(cases) = 514; N(controls) = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children.
We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10(-3)) and decreased fasting serum insulin levels (β = -0.10 μU/mL; P = 1.21 × 10(-3)), respectively.
Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.
最近的全基因组关联研究（GWAS）和之前的定位连锁研究已经确定了 50 多个与肥胖相关的单核苷酸多态性（SNP），这些 SNP 主要存在于欧洲人群中。本研究旨在评估其中一些 SNP 对墨西哥儿童肥胖风险和相关代谢特征变异的贡献。
在 1463 名学龄墨西哥儿童（病例组 n=514；对照组 n=949）中，检测 FTO、NPC1、ENPP1、NEGR1、GNPDA2 和 MC4R 基因内或附近的 6 个与肥胖相关的欧洲 SNP 与肥胖风险的相关性。在 1171 名非肥胖墨西哥儿童的亚组中，我们还评估了这些 SNP 对体重指数（BMI）、空腹血清胰岛素水平、空腹血浆葡萄糖水平、总胆固醇和甘油三酯水平变异的影响。
我们发现 GNPDA2 rs10938397 对肥胖风险有显著影响（比值比[OR] = 1.30；P = 1.34×10-3）。此外，我们发现肥胖风险或 BMI 变异与以下 SNP 之间存在名义关联：ENPP1 rs7754561、MC4R rs17782313 和 NEGR1 rs2815752。重要的是，MC4R rs17782313 和 NPC1 rs1805081 的风险等位基因均显著影响空腹血糖水平升高（β=0.36mmol/L；P = 1.47×10-3）和空腹血清胰岛素水平降低（β=-0.10μU/mL；P = 1.21×10-3）。
本研究结果提示，之前在欧洲人群中报道的一些与肥胖相关的 SNP 也与墨西哥儿童的肥胖风险或代谢定量特征相关。重要的是，我们发现了 MC4R 与空腹血糖水平以及 NPC1 与空腹胰岛素水平之间的新关联。
