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
Laboratory for Diabetic Nephropathy, SNP Research Centre, Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Diabetologia. 2005 Jul;48(7):1315-22. doi: 10.1007/s00125-005-1797-0. Epub 2005 Jun 4.
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.
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.
CONCLUSIONS/INTERPRETATION: These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.
目的/假设：尽管遗传易感性在2型糖尿病发病机制中起重要作用，但大多数影响2型糖尿病易感性的基因尚未被鉴定。已知Krüppel样转录因子在发育和细胞分化中起重要作用，最近也被认为与2型糖尿病发病机制有关。本研究旨在检测日本一大群受试者中，Krüppel样因子（KLF）家族成员编码基因中的单核苷酸多态性（SNP）与2型糖尿病的关联。
我们使用PCR-Invader分析方法，对2型糖尿病患者和普通人群中的12个KLF基因中的33个SNP位点进行基因分型。我们还检测了KLF7过表达对3T3-L1细胞脂肪生成的影响。
我们发现KLF7中的一个SNP与2型糖尿病之间存在显著关联（A与C比较：经Bonferroni校正后p=0.004，优势比=1.59，95%可信区间1.27-2.00）。随着3T3-L1脂肪细胞分化，Klf7的表达降低，而KLF7的过表达导致3T3-L1细胞脂肪生成受到显著抑制。
结论/解读：这些结果表明，编码KLF7的基因是赋予2型糖尿病遗传易感性的一个新候选基因。
