Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy

Abstract

OBJECTIVE - Recently, variants in the TCF7L2 gene have been reported to be associated with type 2 diabetes across multiple Europid populations, but only one small sample of African-American type 2 diabetic patients has been examined. Our objective was to investigate the importance of TCF7L2 in a larger African-American case-control population. RESEARCH DESIGN AND METHODS - We investigated single nucleotide polymorphisms (SNPs) in six known type 2 diabetes genes in 577 African-American case subjects with type 2 diabetes enriched for nephropathy and 596 African-American control subjects. Additionally, we genotyped 70 ancestry-informative markers (AIMs) to apply adjustments for differences in ancestral proportions. RESULTS - The most significant associations were observed with TCF7L2 intron 3 SNPs rs7903146 (additive P = 4.10 × 10-6, odds ratio [OR] 1.51; admixture-adjusted P a = 3.77 × 10-6) and rs7901695 (P = 0.001, OR 1.30; Pa = 0.003). The 2-SNP haplotype containing these SNPs was also associated with type 2 diabetes (P = 3 × 10-5). Modest associations were also seen with TCF7L2 intron 4 SNPs rs7895340, rs11196205, and rs12255372 (0.01 < P < 0.05; 0.03 < Pa < 0.08), as well as with ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2 (KCNJ11) and hepatocyte nuclear factor 4-α (HNF4A) SNPs (0.01 < P < 0.05; 0.01 < Pa < 0.41). No significant associations were detected with genotyped calpain 10 (CAPN10), peroxisome proliferator-activated receptor γ (PPARG), and transcription factor 1 (TCF1) SNPs. CONCLUSIONS - This study indicates that variants in the TCF7L2 gene significantly contribute to diabetes susceptibility in African-American populations. © 2007 by the American Diabetes Association.