Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes

• Published in: Diabetologia Vol. 48; no. 7; pp. 1315 - 1322
• Main Authors: Kanazawa, A, Kawamura, Y, Sekine, A, Iida, A, Tsunoda, T, Kashiwagi, A, Tanaka, Y, Babazono, T, Matsuda, M, Kawai, K, Iiizumi, T, Fujioka, T, Imanishi, M, Kaku, K, Iwamoto, Y, Kawamori, R, Kikkawa, R, Nakamura, Y, Maeda, S
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01-07-2005
• Subjects: 3T3 Cells; Animals; Chromosome Mapping; Diabetes Mellitus, Type 2 - genetics; DNA-Binding Proteins - genetics; Genetic Predisposition to Disease; Genotype; Humans; Introns - genetics; Kruppel-Like Transcription Factors; Mice; Multigene Family; Odds Ratio; Polymorphism, Single Nucleotide; Reference Values; Transcription Factors - genetics
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-005-1797-0

Although genetic susceptibility plays an important role in the pathogenesis of type 2 diabetes, most of the genes that influence susceptibility to type 2 diabetes have yet to be identified. Krüppel-like transcription factors are known to play important roles in development and cell differentiation, and have recently been implicated in the pathogenesis of type 2 diabetes. The present study aimed to examine the associations of single nucleotide polymorphisms (SNPs) in genes encoding members of the Krüppel-like-factor (KLF) family with type 2 diabetes in a large cohort of Japanese subjects.
We genotyped 33 SNP loci found in 12 KLF genes in subjects with type 2 diabetes and in subjects from the general population using the PCR-Invader assay. We also examined the effects of the overexpression of KLF7 on adipogenesis in 3T3-L1 cells.
We identified a significant association between an SNP in KLF7 and type 2 diabetes (A vs C: p=0.004 after Bonferroni's correction, odds ratio=1.59, 95% CI 1.27-2.00). The expression of Klf7 decreased in response to the differentiation of 3T3-L1 adipocytes, and the overexpression of KLF7 resulted in significant inhibition of adipogenesis in 3T3-L1 cells.
These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.