title: Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program.
abstract: OBJECTIVE
  To assess associations and genotype × treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits.
  
  
  METHODS
  Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment.
  
  
  RESULTS
  The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all Pinteraction < 0.05).
  
  
  CONCLUSIONS
  This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.
authors.affiliation: Department of Statistics, Department of Biostatistics and Epidemiology, The Biostatistics Center, George Washington University, Rockville, Maryland, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Pan
authors.forename: Linda M
authors.initials: LM
authors.lastname: Delahanty
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000517:prevention & control; D004032:Diet; D015444:Exercise; D005260:Female; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008019:Life Style; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012306:Risk; D015431:Weight Loss / Q000235:genetics*
chemical_list: D007004:Hypoglycemic Agents; D044105:Receptor, Melanocortin, Type 4; D008687:Metformin