Yoshida Tetsuro, Kato Kimihiko, Yokoi Kiyoshi, Oguri Mitsutoshi, Watanabe Sachiro, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Aoyagi Yukitoshi, Nozawa Yoshinori, Yamada Yoshiji
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe;
Exp Ther Med. 2010 Jan;1(1):137-145. doi: 10.3892/etm_00000023. Epub 2010 Jan 1.
Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 5835 unrelated Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150 polymorphisms were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). The genotypes for these polymorphisms were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The χ(2) test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that two different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with or without hypertension or diabetes mellitus: the A→G (Lys625Arg) polymorphism of CDH4 (rs6142884) in individuals without diabetes mellitus, and the C→T polymorphism of PTPRN2 (rs1638021) in individuals with hypertension and diabetes mellitus. No polymorphism was significantly associated with CKD in individuals with or without hypertension, in those with diabetes mellitus, or in those without hypertension or diabetes mellitus. Stratification of subjects based on hypertension or diabetes mellitus may thus be fundamental to achieving the personalized prevention of CKD with the use of genetic information.
高血压和糖尿病是慢性肾脏病（CKD）的重要危险因素。本研究的目的是识别在有或无高血压或糖尿病的个体中赋予CKD易感性的基因变异，从而有助于分别对这些个体进行CKD的个性化预防。研究人群包括5835名无亲缘关系的日本个体，其中1763名患有CKD，4072名作为对照。通过使用基因芯片人类映射500K阵列集（Affymetrix）对缺血性中风和心肌梗死进行全基因组关联研究，选择了150个多态性位点。这些多态性位点的基因型通过将聚合酶链反应和序列特异性寡核苷酸探针与悬浮阵列技术相结合的方法来确定。χ²检验、对协变量进行调整的多变量逻辑回归分析以及逐步向前选择程序显示，有两个不同的多态性位点与有或无高血压或糖尿病的个体中CKD的患病率显著相关（P<0.005）：在无糖尿病的个体中，CDH4基因的A→G（Lys625Arg）多态性（rs6142884）；在患有高血压和糖尿病的个体中，PTPRN2基因的C→T多态性（rs1638021）。在有或无高血压的个体、患有糖尿病的个体或无高血压和糖尿病的个体中，没有多态性位点与CKD显著相关。基于高血压或糖尿病对受试者进行分层可能是利用基因信息实现CKD个性化预防的基础。
