Aim/hypothesis
A strong association between susceptibility to type 2 diabetes and common variants of transcription factor 7-like 2 (TCF7L2), encoding an enteroendocrine transcription factor involved in glucose homeostasis, has been reported in three different
populations (Iceland, Denmark and USA) by Grant et al. We aimed to replicate these findings in a Dutch cohort.
Methods
We analysed the genotypes of two intronic single nucleotide polymorphisms (SNPs) in TCF7L2 gene in 502 unrelated type 2 diabetes patients and in a set of healthy controls (n = 920). The two SNPs showed almost complete linkage disequilibrium (D′ = 0.91).
Results
We were able to replicate the previously reported association in our Breda cohort. The minor alleles of both variants were
significantly over-represented in cases (odds ratio [OR] 1.29, 95% CI 1.09–1.52,
p = 3 ×10 - 3 p = 3 \times 10^{{ - 3}} for rs12255372; OR 1.41, 95% CI 1.19–1.66,
p = 4.4 ×10 - 5 p = 4.4 \times 10^{{ - 5}} for rs7903146). In addition,
TCF7L2 haplotypes were analysed for association with the disease. The analysis of haplotypes did not reveal any strong association
beyond that expected from analysing individual SNPs. The
TT haplotype carrying the minor alleles was more frequent among cases (OR 1.38,
p = 2.7 ×10 - 3 p = 2.7 \times 10^{{ - 3}} ).
Conclusions/interpretation
Our data strongly confirm that variants of the TCF7L2 gene contribute to the risk of type 2 diabetes. The population-attributable risk from this factor in the Dutch type 2 diabetes
population is 10%.
Keywords Association - Genetics - SNP - Susceptibility - TCF4 - TCF7L2 - Type 2 diabetes - Variant
M. H. Hofker and C. Wijmenga contributed equally.