Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children.
Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children.
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DOI：
10.1186/1471-2350-14-21
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发表时间：
2013-02-01
影响因子：
--
通讯作者：
Bonnefond A
中科院分区：
文献类型：
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作者：
Mejía-Benítez A;Klünder-Klünder M;Yengo L;Meyre D;Aradillas C;Cruz E;Pérez-Luque E;Malacara JM;Garay ME;Peralta-Romero J;Flores-Huerta S;García-Mena J;Froguel P;Cruz M;Bonnefond A
最近的全基因组关联研究（GWAS）和以前的位置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），主要是在欧洲。我们的目的是评估墨西哥儿童中这些SNPs对肥胖风险和相关代谢特征变化的贡献。在1，463名墨西哥学龄儿童中检测了FTO、NPC 1、ENPP 1、NEGR 1、GNPDA 2和MC 4 R基因中或附近的6个欧洲肥胖相关SNP与肥胖风险的相关性（N例= 514; N对照= 949）。我们还评估了这些SNPs对1,171名非肥胖墨西哥儿童的体重指数（BMI）、空腹血清胰岛素水平、空腹血糖水平、总胆固醇和甘油三酯水平变化的影响。我们发现GNPDA 2 rs 10938397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变化与以下SNP之间存在名义上的关联：ENPP 1 rs7754561，MC 4 R rs 17782313和NEGR 1 rs 2815752。重要的是，MC 4 R rs 17782313和NPC 1 rs 1805081的高危等位基因分别对空腹血糖水平升高（β = 0.36 mmol/L; P = 1.47 × 10-3）和空腹血清胰岛素水平降低（β =-0.10 μU/mL; P = 1.21 × 10-3）有显著影响。我们目前的研究结果表明，一些肥胖相关的SNPs以前在欧洲人中报道也与墨西哥儿童肥胖的风险，或代谢的数量性状。重要的是，我们发现MC 4 R与空腹血糖水平之间以及NPC 1与空腹胰岛素水平之间存在新的关联。
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 (Ncases = 514; Ncontrols = 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.
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