B Xi1, F Takeuchi2, G R Chandak3, N Kato2, H W Pan4,5, D H Zhou6, H Y Pan7, J Mi8. 1. 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. 2. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. 3. Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, India. 4. Department of Ophthalmology, Medical College, Jinan University, Guangzhou, China. 5. Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, People's Republic of China. 6. Department of Endocrinology, Linyi People's Hospital, Linyi, People's Republic of China. 7. Department of Epidemiology and Biostatistics, Guangdong Medical College, Dongwan, People's Republic of China. 8. Department of Epidemiology, Capital Institute of Pediatrics, 2 Ya Bao Road, Beijing, 100020, People's Republic of China. jiemi@vip.163.com.
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.
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.
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