Common Polymorphism near the MC4R Gene Is Associated with Type 2 Diabetes: Data from a Meta-Analysis of 123,373 Individuals

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Xi, B.; Takeuchi, Fumihiko; Chandak, Giriraj R.; Kato, Norihiro; Pan, H. W.; AGEN-T2D Consortium, [; Linda S. Adair, Member; ]; Zhou, D. H.; & Pan, H. Y., et al. (2012). Common Polymorphism near the MC4R Gene Is Associated with Type 2 Diabetes: Data from a Meta-Analysis of 123,373 Individuals. Diabetologia, 55(10), 2660-2666.

Abstract

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.
METHODS: 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.
RESULTS: 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.

URL

http://dx.doi.org/10.1007/s00125-012-2655-5

Reference Type

Journal Article

Year Published

2012

Journal Title

Diabetologia

Author(s)

Xi, B.
Takeuchi, Fumihiko
Chandak, Giriraj R.
Kato, Norihiro
Pan, H. W.
AGEN-T2D Consortium, [
Linda S. Adair, Member
]
Zhou, D. H.
Pan, H. Y.
Mi, J.