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, Yandiswaen_ZA
dc.contributor.authorKengne, Andreen_ZA
dc.contributor.authorErasmus, Rajiven_ZA
dc.contributor.authorMatsha, Tandien_ZA
dc.date.accessioned2015-11-27T09:33:42Z
dc.date.available2015-11-27T09:33:42Z
dc.date.issued2014en_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.identifier.apacitationVergotine, Z., Yako, Y., Kengne, A., Erasmus, R., & Matsha, T. (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. <i>BMC Genetics</i>, http://hdl.handle.net/11427/15403en_ZA
dc.identifier.chicagocitationVergotine, Zelda, Yandiswa Yako, Andre Kengne, Rajiv Erasmus, and Tandi Matsha "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." <i>BMC Genetics</i> (2014) http://hdl.handle.net/11427/15403en_ZA
dc.identifier.citationVergotine, Z., Yako, Y. Y., Kengne, A. P., Erasmus, R. T., & Matsha, T. E. (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.en_ZA
dc.identifier.ris TY - Journal Article AU - Vergotine, Zelda AU - Yako, Yandiswa AU - Kengne, Andre AU - Erasmus, Rajiv AU - Matsha, Tandi AB - BACKGROUND: 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. DA - 2014 DB - OpenUCT DO - 10.1186/1471-2156-15-10 DP - University of Cape Town J1 - BMC Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - 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 TI - 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 UR - http://hdl.handle.net/11427/15403 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15403
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2156-15-10
dc.identifier.vancouvercitationVergotine Z, Yako Y, Kengne A, Erasmus R, Matsha T. 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. 2014; http://hdl.handle.net/11427/15403.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2014 Vergotine et al.; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Geneticsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcgenet/en_ZA
dc.subject.otherIRS1 Gly972Argen_ZA
dc.subject.otherPPARG Pro12Alaen_ZA
dc.subject.otherInsulin resistanceen_ZA
dc.subject.otherType 2 diabetesen_ZA
dc.subject.otherAfricaen_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.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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