Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa

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dc.contributor.authorVergotine, Zeldaen_ZA
dc.contributor.authorYako, Yandiswa Y.en_ZA
dc.contributor.authorKengne, Andre P.en_ZA
dc.contributor.authorErasmus, Rajiv T.en_ZA
dc.contributor.authorMatsha, Tandi E.en_ZA
dc.date.accessioned2014-08-19T06:12:49Z
dc.date.available2014-08-19T06:12:49Z
dc.date.issued2014-01
dc.date.updated2014-01-24T12:59:17Z
dc.descriptionPlease cite as follows: Vergotine, Z. et al. 2014. Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa, BMC Genetics, 15(1):10, doi:10.1186/1471-2156-15-10.en_ZA
dc.descriptionThe original publication is available at http://www.biomedcentral.com/1471-2156/15/10en_ZA
dc.description.abstractBackground: The peroxisome proliferator-activated receptor gamma (PPARG), Pro12Ala and the insulin receptor substrate (IRS1), Gly972Arg confer opposite effects on insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the independent and joint effects of PPARG Pro12Ala and IRS1 Gly972Arg on markers of insulin resistance and T2DM in an African population with elevated risk of T2DM. In all 787 (176 men) mixed-ancestry adults from the Bellville-South community in Cape Town were genotyped for PPARG Pro12Ala and IRS1 Gly972Arg by two independent laboratories. Glucose tolerance status and insulin resistance/sensitivity were assessed. Results: Genotype frequencies were 10.4% (PPARG Pro12Ala) and 7.7% (IRS1 Gly972Arg). Alone, none of the polymorphisms predicted prevalent T2DM, but in regression models containing both alleles and their interaction term, PPARG Pro12 conferred a 64% higher risk of T2DM. Furthermore PPARG Pro12 was positively associated in adjusted linear regressions with increased 2-hour post-load insulin in non-diabetic but not in diabetic participants. Conclusion: The PPARG Pro12 is associated with insulin resistance and this polymorphism interacts with IRS1 Gly972Arg, to increase the risk of T2DM in the mixed-ancestry population of South Africa. Our findings require replication in a larger study before any generalisation and possible application for risk stratification.en_ZA
dc.description.versionPublishers' Versionen_ZA
dc.format.extent8 pages
dc.identifier.citationVergotine, Z. et al. 2014. Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa, BMC Genetics, 15(1):10, doi:10.1186/1471-2156-15-10.en_ZA
dc.identifier.issn1471-2156 (online)en_ZA
dc.identifier.otherdoi:10.1186/1471-2156-15-10en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/95542
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Centralen_ZA
dc.rights.holderZelda Vergotine et al.; licensee BioMed Central Ltd.en_ZA
dc.subjectInsulin -- Receptorsen_ZA
dc.subjectNuclear receptors (Biochemistry)en_ZA
dc.subjectInsulin resistanceen_ZA
dc.titleProliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africaen_ZA
dc.typeArticleen_ZA
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