Research
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' affiliations
Zelda Vergotine, 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
Andre Pascal Kengne, National Collaborative Research Programme for Cardiovascular and Metabolic Diseases, South African Medical Research Council, Tygerberg and University of Cape Town, South Africa
Rajiv Timothy Erasmus, Division of Chemical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa
Tandi Edith Matsha, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa
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Date published: 2014-05-12
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