Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort.
OBJECTIVE
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, [Formula: see text] for rs12255372; OR 1.41, 95% CI 1.19-1.66, [Formula: see text] 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, [Formula: see text]).


CONCLUSIONS
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%.
van Vliet-Ostaptchouk
J V
JV
Department of Molecular Genetics, Maastricht University, Universiteitssingel 50 (UNS50/11), P.O. Box 616, 6200 MD, Maastricht, the Netherlands.
Shiri-Sverdlov
R
R
Zhernakova
A
A
Strengman
E
E
van Haeften
T W
TW
Hofker
M H
MH
Wijmenga
C
C
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics* / Q000502:physiology; D058118:Transcription Factor 7-Like 2 Protein
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein