title: Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China. xibo2007@126.com.
authors.forename: B
authors.initials: B
authors.lastname: Xi
authors.affiliation: Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Takeuchi
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India.
authors.forename: G R
authors.initials: GR
authors.lastname: Chandak
authors.affiliation: Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Ophthalmology, Medical College, Jinan University, Guangzhou, China.|Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, People's Republic of China.
authors.forename: H W
authors.initials: HW
authors.lastname: Pan
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi, People's Republic of China.
authors.forename: D H
authors.initials: DH
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology and Biostatistics, Guangdong Medical College, Dongwan, People's Republic of China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Pan
authors.affiliation: Department of Epidemiology, Capital Institute of Pediatrics, 2 Ya Bao Road, Beijing, 100020, People's Republic of China. jiemi@vip.163.com.
authors.forename: J
authors.initials: J
authors.lastname: Mi
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4