title: Replication of association between a common variant near melanocortin-4 receptor gene and obesity-related traits in Asian Sikhs.
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.
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Latonya F
authors.initials: LF
authors.lastname: Been
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.forename: Sarju K
authors.initials: SK
authors.lastname: Ralhan
authors.forename: Gurpreet S
authors.initials: GS
authors.lastname: Wander
authors.forename: Narinder K
authors.initials: NK
authors.lastname: Mehra
authors.forename: Jairup
authors.initials: J
authors.lastname: Singh
authors.forename: John J
authors.initials: JJ
authors.lastname: Mulvihill
authors.forename: Dharambir K
authors.initials: DK
authors.lastname: Sanghera
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D007333:Insulin Resistance / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference / Q000208:ethnology / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C470072:MC4R protein, human; C116385:MLXIPL protein, human; D044105:Receptor, Melanocortin, Type 4