Polymorphisms in a number of genes have consistently been associated with type 2 diabetes in various Caucasian populations. Little, however, is known of the association between these genetic risk markers and type 2 diabetes in sub-Saharan African subjects. The aim of the current study was to determine the association between common variants in the PPARG, KCNJ11, TCF7L2, FTO and HHEX genes in African (black) subjects of Zulu descent in KwaZulu-Natal, South Africa. The association between type 2 diabetes and rs1801282 (PPARG), rs5215 (KCNJ11), rs12255372 (TCF7L2), rs7903146 (TCF7L2) rs9939609 (FTO) and rs1111875 (HHEX) was determined in 178 South African Zulu subjects and 200 healthy ethnically matched control subjects. rs1801282 (PPARG) and rs5215 (KCNJ11) were not found to be present in either the subjects with type 2 diabetes or the control subjects. No association between rs12255372 (TCF7L2), rs9939609 (FTO) and type 2 diabetes was found. Heterozygosity at rs7903146 (TCF7L2) was associated with type 2 diabetes (odds ratio 1.84, 95% confidence interval: 1.19–2.83, p=0.0035). Decreased frequency of homozygosity for the common allele at rs7903146 (TCF7L2) was observed in subjects with type 2 diabetes (odds ratio 0.54, 95% confidence interval: 0.34–0.84; p=0.0043). There was an increased frequency of C allele homozygosity in subjects with type 2 diabetes at rs1111875 (HHEX), of borderline significance (odds ratio 1.54, 95% confidence interval 0.97–2.44, p=0.052). Subjects with type 2 diabetes harbouring one or more of the risk alleles did not differ from those without genetic variation at the loci studied, with respect to age at diagnosis, blood pressure, body mass index or serum lipid levels. We conclude that risk polymorphisms identified in Caucasian populations are not associated with type 2 diabetes in this group of South African subjects of Zulu descent, with the exception of rs7903146 (TCF7L2). The genetic risk for type 2 diabetes in sub-Saharan African subjects may reside in other, as yet unidentified, genes

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