Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population.
OBJECTIVE
The transcription factor 7-like 2 gene (TCF7L2) has been shown to be strongly associated with an increased risk of type 2 diabetes in white populations. To further investigate the involvement of TCF7L2 in conferring susceptibility to type 2 diabetes, we examined the association of TCF7L2 polymorphisms with type 2 diabetes in a Japanese population.


METHODS
We analysed four SNPs (rs12255372, rs7903146, rs7901695 and rs11196205) and one tetranucleotide repeat polymorphism (DG10S478) in 1,630 Japanese subjects with type 2 diabetes and 1,064 control subjects.


RESULTS
All investigated polymorphisms were significantly associated with type 2 diabetes, and rs12255372 showed the strongest association (T vs G, chi2 = 9.20, p = 0.0024, odds ratio = 1.70, 95% CI = 1.20-2.41), although the frequency of the risk allele in our population was much lower than that in white populations. The microsatellite polymorphism showed an almost complete linkage disequilibrium to rs1255372 when the alleles with longer repeats (+8, +12) were considered as minor alleles and showed an association with type 2 diabetes (chi2 = 5.34, p = 0.021, odds ratio = 1.50, 95% CI = 1.06-2.12).


CONCLUSIONS
These results indicate that TCF7L2 might be a strong candidate for conferring susceptibility to type 2 diabetes across different ethnicities.
Hayashi
T
T
Laboratory for Diabetic Nephropathy, SNP Research Centre, The Institute of Physical and Chemical Research, Yokohama, Kanagawa 230-0045, Japan.
Iwamoto
Y
Y
Kaku
K
K
Hirose
H
H
Maeda
S
S
D000368:Aged; D044466:Asian People; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005006:Ethnicity / Q000706:statistics & numerical data; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
D004247:DNA; D006442:Glycated Hemoglobin; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; C544894:TCF7L2 protein, human