Single nucleotide polymorphisms in the gene encoding Kruppel-like factor 7 are associated with type 2 diabetes
Single nucleotide polymorphisms in the gene encoding Kruppel-like factor 7 are associated with type 2 diabetes
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DOI：
10.1007/s00125-005-1797-0
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发表时间：
2005-07-01
期刊：
影响因子：
8.2
通讯作者：
Maeda, S
中科院分区：
文献类型：
--
作者：
Kanazawa, A;Kawamura, Y;Maeda, S
目的/假设：虽然遗传易感性在2型糖尿病的发病机制中起着重要作用，但影响2型糖尿病易感性的大多数基因尚未被确定。Kruppel样转录因子在发育和细胞分化中起重要作用，最近被认为与2型糖尿病的发病机制有关。本研究的目的是研究编码Kruppel样因子（KLF）家族成员基因的单核苷酸多态性（SNP）与日本大队列2型糖尿病的关系。研究方法：我们使用PCR-Invader分析法对2型糖尿病患者和普通人群中12个KLF基因中的33个SNP位点进行了基因分型。我们还研究了KLF 7过表达对3 T3-L1细胞脂肪形成的影响。结果如下：我们确定了KLF 7中的SNP与2型糖尿病之间的显著相关性（A vs C：经Bonferroni校正后p=0.004，比值比=1.59，95%CI 1.27-2.00）。随着3 T3-L1脂肪细胞的分化，Klf 7的表达水平降低，过表达Klf 7可显著抑制3 T3-L1细胞的脂肪形成。结论/解释：这些结果表明，编码KLF 7的基因是赋予2型糖尿病遗传易感性的新候选基因。
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. Kruppel-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 Kruppel-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.