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

A Kanazawa; Y Kawamura; A Sekine; A Iida; T Tsunoda; A Kashiwagi; Y Tanaka; T Babazono; M Matsuda; K Kawai; T Iiizumi; T Fujioka; M Imanishi; K Kaku; Y Iwamoto; R Kawamori; R Kikkawa; Y Nakamura; S Maeda

doi:10.1007/s00125-005-1797-0

PubMed · 15937668

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

A Kanazawa·Y Kawamura·A Sekine·A Iida·T Tsunoda·A Kashiwagi·Y Tanaka·T Babazono·M Matsuda·K Kawai·T Iiizumi·T Fujioka·M Imanishi·K Kaku·Y Iwamoto·R Kawamori·R Kikkawa·Y Nakamura·S Maeda

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Abstract

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.

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3T3 Cells Animals Chromosome Mapping DNA-Binding Proteins Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Genotype Humans Introns Kruppel-Like Transcription Factors Mice Multigene Family Odds Ratio Polymorphism, Single Nucleotide Reference Values Transcription Factors Comparative Study Journal Article Research Support, Non-U.S. Gov't

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A Kanazawa, Y Kawamura, A Sekine, A Iida, T Tsunoda, A Kashiwagi, Y Tanaka, T Babazono, M Matsuda, K Kawai, T Iiizumi, T Fujioka, M Imanishi, K Kaku, Y Iwamoto, R Kawamori, R Kikkawa, Y Nakamura, S Maeda. 2005-06-04. Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes.. https://doi.org/10.1007/s00125-005-1797-0

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