Department of Maternal and Child Health Care, School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Diabetologia. 2012 Oct;55(10):2660-2666. doi: 10.1007/s00125-012-2655-5. Epub 2012 Aug 7.
AIMS/HYPOTHESIS: Genome-wide association studies have shown that variants near the melanocortin 4 receptor gene (MC4R) (rs17782313 and rs12970134) are associated with risk of obesity in Europeans. As obesity is associated with an increased risk of type 2 diabetes, many studies have investigated the association between polymorphisms near the MC4R gene and type 2 diabetes risk across different ethnic populations, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of variants near MC4R with type 2 diabetes risk.
Published literature from PubMed and Embase was retrieved. All studies that evaluated the association of at least one of the two MC4R polymorphism(s) with type 2 diabetes were included in the study. Pooled ORs with 95% CIs were calculated using the fixed-effects model.
A total of 19 studies (comprising 34,195 cases and 89,178 controls) of the rs17782313 polymorphism (or its proxy rs12970134) were included in the meta-analysis. The results indicated that the rs17782313 polymorphism was significantly associated with type 2 diabetes risk among the overall study population (OR 1.10, 95% CI 1.07, 1.13, p = 2.83 × 10(-12) [Z test], I(2) = 9.1%, p = 0.345 [heterogeneity]). The association remained significant even after adjustment for body mass index (BMI) (OR 1.06, 95% CI 1.03, 1.09, p = 2.14 × 10(-5) [Z test], I(2) = 4.9%, p = 0.397 [heterogeneity]). Further sensitivity analysis confirmed the statistically significant association of rs17782313 polymorphism with type 2 diabetes, and no publication bias was detected.
CONCLUSIONS/INTERPRETATION: The present meta-analysis confirmed the significant association of the rs17782313 polymorphism near the MC4R gene with type 2 diabetes risk, which was independent of BMI.
目的/假设：全基因组关联研究表明，黑素皮质素 4 受体基因（MC4R）（rs17782313 和 rs12970134）附近的变异与欧洲人肥胖的风险有关。由于肥胖与 2 型糖尿病的风险增加有关，许多研究调查了 MC4R 基因附近的多态性与不同种族人群 2 型糖尿病风险之间的关联，结果不一致。在这项研究中，我们进行了荟萃分析以阐明 MC4R 附近变体与 2 型糖尿病风险的关联。
从 PubMed 和 Embase 检索已发表的文献。所有评估这两种 MC4R 多态性（或其替代物 rs12970134）中至少一种与 2 型糖尿病关联的研究都包含在研究中。使用固定效应模型计算合并 OR 及其 95%CI。
共纳入 19 项研究（共包含 34195 例病例和 89178 例对照）评估 rs17782313 多态性（或其替代物 rs12970134）的荟萃分析。结果表明，rs17782313 多态性与总体研究人群的 2 型糖尿病风险显著相关（OR 1.10，95%CI 1.07，1.13，p = 2.83×10(-12)[Z 检验]，I(2) = 9.1%，p = 0.345[异质性]）。即使在调整体重指数（BMI）后，这种关联仍然显著（OR 1.06，95%CI 1.03，1.09，p = 2.14×10(-5)[Z 检验]，I(2) = 4.9%，p = 0.397[异质性]）。进一步的敏感性分析证实了 rs17782313 多态性与 2 型糖尿病的统计学显著关联，且未检测到发表偏倚。
结论/解释：本荟萃分析证实了 MC4R 基因附近的 rs17782313 多态性与 2 型糖尿病风险显著相关，且与 BMI 无关。
