Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women

Abstract

Common variants of TCF7L2, encoding a β-cell-expressed transcription factor, are strongly associated with increased risk of type 2 diabetes (T2D). We examined this association using both prospective and case-control designs. A total of 2,676 healthy European white middle-aged men from the prospective NPHSII (158 developed T2D over 15 years surveillance) were genotyped for two intronic SNPs [rs 7903146 (IVS3C∈>∈T) and rs12255372 (IVS4G∈>∈T)] which showed strong linkage disequilibrium (D∈=∈0.88, p∈ <0.0001. A similar effect was observed in 919 T2D Indian Asians [OR∈=∈1.50 (1.14-1.99) and 1.64 (1.03-2.63) p∈=∈0.003] and 385 Afro-Caribbean subjects [OR∈=∈1.25 (0.90-1.75) and 1.32 (0.74-2.33) p∈=∈0.17] compared to non-diabetic ethnically matched subjects from South London. Weaker associations were found for the IVS4G∈>∈T in all studies. Linkage disequilibrium between the two SNPs was high in Indian Asians (D∈=∈0.94), but much weaker in Afro-Caribbeans (D∈=∈0.17) and haplotype frequencies differed markedly in this group. These results extend previous observations to other ethnic groups, and strongly confirm that TCF7L2 genotype is a major risk factor for development of T2D. © 2006 Springer-Verlag.