Abstract 4115: Transcription factor 7-like-2 polymorphisms and risk of Type 2 Diabetes in Indian Asians and Northern Europeans
Background Indian Asians (IA) are at increased risk of Type 2 Diabetes (T2D) compared to other populations. In the UK, T2D prevalence is 4 times higher among IA compared with Northern Europeans (NE). Recent studies in Caucasian populations have suggested an association of allelic variation in the Transcription factor 7-like-2 (TCF7L2) gene with T2D. The purpose of this study was to i. replicate previous finding in NE and ii. investigate whether TCF7L2 is associated with T2D in IA, and accounts for their increased risk of T2D.
Methods We investigated 1006 IA (271 T2D+, 735 T2D-), and 1005 NE (177 T2D+, 828 T2D-) men aged 35– 65 yrs. Based on the LD structure of SNPs in the TCF7L2 interval in HapMap CEU samples, we identified two SNP markers (rs4506565 and rs6585200) for which we had previously developed assays, and which showed moderate to strong pairwise r2 with the reported SNP markers in TCF7L2. All participants were genotyped for rs4506565 and rs6585200.
Results The allele frequencies in T2D cases and controls, and odds ratios for the association between genotype and T2D status are shown (table⇓). SNP rs4506565 was associated with T2D in both IA and NE, with both effects in the expected direction. We did not see significant association between rs6585200 and T2D, however our data is consistent with the smaller effect expected at this site. There was no increase in the prevalence of either rs4506565 or rs6585200 amongst IA compared to NE.
Conclusions This study is the first to demonstrate that TCF7L2 is associated with T2D in IA, and further validates the association with T2D in Caucasian populations TCF7L2. The prevalence of SNPs associated with T2D is similar amongst IA and NE, and TCF7L2 does not account for the excess risk of T2D amongst Asians.