Association of genetic variants in the HNF4A and HNF1B genes with early onset Type 2 diabetes mellitus in the Indo and Afro-Trinidadian populations

ABSTRACT

OBJECTIVE: To determine if variation in HNF4A, HNF1B and PAX4 genes is associated with increased risk of early onset Type 2 diabetes mellitus (T2DM) in Indo and Afro-Trinidadians. DESIGN AND METHODS: The promoter, exons and flanking intronic regions of the HFN4A, HNF1B and PAX4 genes were sequenced in 167 T2DM and 61 non-diabetic subjects of South Asian Indian ancestry, and 66 T2DM and 59 non- diabetic subjects of African ancestry. Differences in SNP allele and haplotype frequency between T2DM patients and non-diabetic subjects were calculated, and pairwise linkage disequilibrium was also assessed for regions within these genes. RESULTS: Three variants identified in intron 4 of the HNF4A gene, demonstrated association with early onset T2DM in the Indo-Trinidadian population, rs11574739, P = 0.0032, OR 2.99 (95% CI 1.44-6.22), rs3212194, P = 0.02, OR 2.57 (95% CI 1.17-5.65), rs321219, P = 0.0083, OR 2.72 (95% CI 1.29-5.71). In the HNF1B gene, an intron 7 SNP, rs2269842, was associated with early onset T2DM in both the Indo and Afro-Trinidadian groups, P = 0.012, OR 0.42 (95% CI 0.20-0.87) and, P = 0.012, OR 0.44(95% CI 0.23-0.86) respectively. Both findings are previously unreported. No association was demonstrated with variants typed within the PAX4 gene. CONCLUSIONS: Variants in the HNF4A and HNF1B genes may contribute to increased risk of early onset T2DM in Indo-Trinidadians. HNF1B variants may similarly influence diabetes susceptibility in Afro-Trinidadians. However, further studies are required to fully elucidate the contribution of such variants to the prevalence of diabetes in the Trinidadian population.