Yoshida Tetsuro, Kato Kimihiko, Yokoi Kiyoshi, Watanabe Sachiro, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Aoyagi Yukitoshi, Nishigaki Yutaka, Suzuki Takao, Nozawa Yoshinori, Yamada Yoshiji
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Int J Mol Med. 2009 Apr;23(4):529-37. doi: 10.3892/ijmm_00000161.
Although diabetes mellitus has been recognized as a risk factor for chronic kidney disease (CKD), genetic factors for predisposition to CKD in individuals with diabetes mellitus remain elucidated. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD among individuals with type 2 diabetes mellitus. The study population comprised 1742 Japanese individuals, including 636 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 1106 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 24 polymorphisms of 22 candidate genes were determined. An initial screen of allele frequencies by the Chi-square test revealed that four polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of CKD in individuals with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) polymorphism of FABP2 (rs1799883) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus.
尽管糖尿病已被公认为慢性肾脏病（CKD）的一个危险因素，但糖尿病患者易患CKD的遗传因素仍有待阐明。本研究的目的是在2型糖尿病患者中鉴定出赋予CKD易感性的基因变异。研究人群包括1742名日本个体，其中有636名CKD患者[估计肾小球滤过率（eGFR）<60 ml/min/1.73 m2]和1106名对照者（eGFR≥60 ml/min/1.73 m2）。测定了22个候选基因的24个多态性的基因型。通过卡方检验对等位基因频率进行初步筛选，结果显示有4个多态性与2型糖尿病患者中CKD的患病率显著相关（错误发现率<0.05）。随后进行多变量逻辑回归分析，并对协变量进行调整以及逐步向前选择程序，结果显示ALOX5AP的8733T→C多态性（rs3803278）、IRAK1的C→T（Ser532Leu）多态性（rs1059703）以及FABP2的2445G→A（Ala54Thr）多态性（rs1799883）与CKD的患病率显著相关（P<0.05）。我们的结果表明，ALOX5AP、IRAK1和FABP2是日本2型糖尿病患者中CKD的易感基因座。
