Yoshida Tetsuro, Kato Kimihiko, Fujimaki Tetsuo, Yokoi Kiyoshi, Oguri Mitsutoshi, Watanabe Sachiro, Metoki Norifumi, Yoshida Hidemi, Satoh Kei, Aoyagi Yukitoshi, Nishigaki Yutaka, Tanaka Masashi, Nozawa Yoshinori, Kimura Genjiro, Yamada Yoshiji
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Clin J Am Soc Nephrol. 2009 May;4(5):883-90. doi: 10.2215/CJN.04350808. Epub 2009 Apr 30.
Although genetic linkage analyses and association studies have implicated several loci and candidate genes in predisposition to chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition have remained uncharacterized. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in Japanese individuals.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population comprised 5217 Japanese individuals (2955 men, 2262 women), including 778 subjects (480 men, 298 women) with CKD [estimated GFR (eGFR), <50 ml min(-1) 1.73 m(-2)] and 4439 controls (2475 men, 1964 women; eGFR, > or =60 ml min(-1) 1.73 m(-2)). The genotypes for 40 polymorphisms of 32 candidate genes were determined.
The chi-square test and multivariable logistic regression analysis with adjustment for covariates revealed that the -219G-->T polymorphism of APOE, the -519A-->G of MMP1, the -866G-->A of UCP2, the -1607/1G-->2G of MMP1, the A-->G (Lys45Glu) of MMP3, the G-->A (Ala163Thr) of AGTR1, the G-->A (Gly670Arg) of PECAM1, and the -55C-->T of UCP3 were significantly (false discovery rate <0.05) associated with CKD. Comparison of allele frequencies of these polymorphisms by the chi-square test between subgroups of CKD and control subjects individually matched for covariates revealed that the -519A-->G of MMP1 and the -866G-->A of UCP2 were significantly (P < 0.05) associated with CKD.
MMP1 and UCP2 may be susceptibility loci for CKD in Japanese individuals. Determination of genotypes for these polymorphisms may prove informative for prediction of genetic risk for CKD.
尽管基因连锁分析和关联研究已表明多个基因座和候选基因与慢性肾脏病（CKD）的易感性有关，但导致这种疾病遗传易感性的基因仍未明确。本研究的目的是在日本人群中鉴定出赋予CKD易感性的基因变异。
设计、研究地点、参与者及测量方法：研究人群包括5217名日本人（2955名男性，2262名女性），其中包括778名CKD患者（480名男性，298名女性）[估计肾小球滤过率（eGFR）<50 ml·min⁻¹·1.73 m⁻²]和4439名对照者（2475名男性，1964名女性；eGFR≥60 ml·min⁻¹·1.73 m⁻²）。测定了32个候选基因的40个多态性位点的基因型。
卡方检验及对协变量进行校正的多变量逻辑回归分析显示，载脂蛋白E（APOE）的-219G→T多态性、基质金属蛋白酶1（MMP1）的-519A→G多态性、解偶联蛋白2（UCP2）的-866G→A多态性、MMP1的-1607/1G→2G多态性、MMP3的A→G（Lys45Glu）多态性、血管紧张素Ⅱ受体1（AGTR1）的G→A（Ala163Thr）多态性、血小板内皮细胞黏附分子1（PECAM1）的G→A（Gly670Arg）多态性以及UCP3的-55C→T多态性与CKD显著相关（错误发现率<0.05）。通过卡方检验对CKD亚组和对照亚组中个体协变量匹配后的这些多态性位点的等位基因频率进行比较，发现MMP1的-519A→G多态性和UCP2的-866G→A多态性与CKD显著相关（P<0.05）。
MMP1和UCP2可能是日本人CKD的易感基因座。对这些多态性位点进行基因型测定可能有助于预测CKD的遗传风险。
