Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population

• Published in: Diabetologia Vol. 50; no. 5; pp. 980 - 984
• Main Authors: Hayashi, T, Iwamoto, Y, Kaku, K, Hirose, H, Maeda, S
• Format: Journal Article
• Language: English
• Published: Berlin Berlin/Heidelberg : Springer-Verlag 01.05.2007; Springer; Springer Nature B.V
• Subjects: Aged; analysis; Asian Continental Ancestry Group; Asian People; Association study; Biological and medical sciences; blood; Chemical research; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA; DNA - blood; DNA - genetics; DNA - isolation & purification; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; epidemiology; Ethnic Groups - statistics & numerical data; Ethnicity; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene polymorphism; Genetic Linkage; Genetic Predisposition to Disease; Genetic testing; genetics; Genotype; Glucose; Glycated Hemoglobin; Glycated Hemoglobin A - analysis; Humans; Internal medicine; isolation & purification; Japan; Japan - epidemiology; Male; Medical sciences; Medicine; Microsatellite marker; Middle Aged; noninsulin-dependent diabetes mellitus; Polymorphism; Polymorphism, Single Nucleotide; Risk Assessment; statistics & numerical data; TCF Transcription Factors; TCF Transcription Factors - genetics; TCF7L2; Transcription factor 7-like 2; Transcription Factor 7-Like 2 Protein; Transcription factors; United States > US; Japan; Endocrinopathy; Type 2 diabetes; TCF7L2; Association study; Metabolic diseases; Transcription factor 7-like 2; Japanese; Gene polymorphism; Sensitivity; Association; Gene; Replication; Microsatellite marker; Transcription factor; Polymorphism
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-007-0618-z

Aims/hypothesis 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. Subjects and 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, χ ² = 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 (χ ² = 5.34, p = 0.021, odds ratio = 1.50, 95% CI = 1.06-2.12). Conclusions/interpretation These results indicate that TCF7L2 might be a strong candidate for conferring susceptibility to type 2 diabetes across different ethnicities.