The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population

• Published in: Diabetic medicine Vol. 25; no. 1; pp. 19 - 26
• Main Authors: Tanahashi, T., Shinohara, K., Keshavarz, P., Yamaguchi, Y., Miyawaki, K., Kunika, K., Moritani, M., Nakamura, N., Yoshikawa, T., Shiota, H., Inoue, H., Itakura, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2008
• Subjects: Adult; Analysis of Variance; Asian Continental Ancestry Group - genetics; association study; Cell Cycle Proteins - analysis; Cell Cycle Proteins - genetics; Diabetes Mellitus, Type 2 - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Insulin - metabolism; Insulin Secretion; Japan - ethnology; Japanese; KLF11; Linkage Disequilibrium; Male; Middle Aged; Original : Genetics; Repressor Proteins - analysis; Repressor Proteins - genetics; Type 2 diabetes; Japan
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/j.1464-5491.2007.02315.x

Aims  Krüppel‐like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12–1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. Methods  By re‐sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. Results  We identified eight variants, including a novel A/C variant on intron 3, but no mis‐sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2–46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. Conclusions  Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations.