title: No evidence for association of insulin receptor substrate-1 Gly972Arg variant with type 2 diabetes mellitus in a mixed-ancestry population of South Africa.
abstract: BACKGROUND
  The most common single-nucleotide polymorphism in the insulin receptor substrate-1 (IRS1) gene is Gly972Arg, which is associated with a 25% increased risk of developing diabetes. The mixed-ancestry population of South Africa (SA) has one of the highest prevalences of type 2 diabetes mellitus (T2DM) in Africa.
  
  
  OBJECTIVE
  To report the frequency of IRS1 Gly972Arg and investigate its associations with cardiometabolic traits.
  
  
  METHODS
  DNA from 856 mixed-ancestry adults drawn from an urban community of Bellville South, Cape Town, SA, was genotyped by two independent laboratories. Oral glucose tolerance tests were performed and cardiometabolic risk factors measured.
  
  
  RESULTS
  A total of 237 (24.7%) participants had T2DM. The IRS1 Gly972Arg variant was present in 7.9% of the individuals studied and only one participant (non-diabetic) carried the homozygous A/A variant. In linear and logistic regression analyses, Gly972Arg was not associated with obesity, insulin resistance/sensitivity or T2DM.
  
  
  CONCLUSIONS
  The prevalence of the Gly972Arg variant in the mixed-ancestry population of SA is comparable to that reported in African Americans, but its presence is not associated with cardiometabolic traits. This suggests that the Gly972Arg variant may not aid diabetes risk evaluation in this setting, nor can such information help explain the high prevalence of diabetes previously reported in this population.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa; Division of Chemical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa. vergotinez@cput.ac.za.
authors.forename: Zelda
authors.initials: Z
authors.lastname: Vergotine
authors.forename: Andre Pascal
authors.initials: AP
authors.lastname: Kengne
authors.forename: Rajiv Timothy
authors.initials: RT
authors.lastname: Erasmus
authors.forename: Tandi Edith
authors.initials: TE
authors.lastname: Matsha
mesh_terms: D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D044468:Native Hawaiian or Pacific Islander; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology; D014505:Urban Population
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D004247:DNA