Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort

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) b...

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Bibliographic Details
Published in:Diabetologia
Main Authors: van Vliet-Ostaptchouk, J.V., Shiri-Sverdlov, R., Zhernakova, A., Strengman, E., van Haeften, T.W., Hofker, M.H., Wijmenga, C.
Format: Article in Journal/Newspaper
Language:English
Published: 2007
Subjects:
association
genetics
SNP
susceptibility
TCF4
TCF7L2
type 2 diabetes
variant
GENE
RISK
Iceland
Online Access:https://hdl.handle.net/11370/bc45af8e-2bca-422d-b0d9-c31d7bb65b22
https://research.rug.nl/en/publications/bc45af8e-2bca-422d-b0d9-c31d7bb65b22
https://doi.org/10.1007/s00125-006-0477-z
https://pure.rug.nl/ws/files/2783688/van_Vliet_2007_Diabetologia.pdf
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Summary: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 = 10(-3) for rs12255372; OR 1.41, 95% CI 1.19-1.66, p = 4.4 x 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 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%.

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