Replication of Association Between a Common Variant Near Melanocortin‐4 Receptor Gene and Obesity‐related Traits in Asian Sikhs |
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| Authors: | Latonya F Been Swapan K Nath Sarju K Ralhan Gurpreet S Wander Narinder K Mehra Jairup Singh John J Mulvihill Dharambir K Sanghera |
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| Institution: | 1. Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA;2. Genetic Epidemiology Unit, Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA;3. Section of Cardiology, Hero Dayanand Medical College and Heart Institute, Ludhiana, India;4. Department of Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India;5. Center for Genetic Disorders, Guru Nanak Dev University, Amritsar, India |
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| Abstract: | Recent genome‐wide association studies (GWAS) in Asian Indians reported strong associations of variants near melanocortin‐4 receptor (MC4R) and MLX interacting protein‐like (MLXIPL) genes with insulin resistance and several obesity‐related quantitative traits (QTs). Here, we evaluated the association of two variants (rs12970134 and rs4450508) near MC4R and a nonsynonymous (Gln241His) variant (rs3812316) in MLXIPL gene with type 2 diabetes (T2D) and obesity‐related QTs in our case–control cohort (n = 1,528; 745 T2D cases and 783 controls) from a Sikh population from North India. We have successfully replicated the association of MC4R (rs12970134) with BMI (P = 0.0005), total weight (WT) (P = 0.001), and waist circumference (WC) (P = 0.001). These associations remained significant after controlling for multiple testing by applying Bonferroni's correction. However, our data did not confirm the association of rs3812316 in the MLXIPL gene with triglyceride (TG) levels. These observations demonstrate that the genetic variation in MC4R locus can have a moderate contribution in the regional fat deposition and development of central obesity in Asian Indians. |
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