Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan.
J Med Genet. 2013 Jun;50(6):410-8. doi: 10.1136/jmedgenet-2013-101518. Epub 2013 Mar 28.
Although genome-wide association studies (GWASs) have implicated several genes in the predisposition to chronic kidney disease (CKD) in Caucasian or African American populations, the genes that confer susceptibility to CKD in Asian populations remain to be identified definitively. We performed a GWAS to identify genetic variants that confer susceptibility to CKD in Japanese individuals.
3851 Japanese individuals from three independent subject panels were examined. Subject panels A, B, and C comprised 252, 910, and 190 individuals with CKD and 249, 838, and 1412 controls, respectively. A GWAS for CKD was performed in subject panel A.
Five single nucleotide polymorphisms (SNPs) at chromosome 3q28, ALPK1, FAM78B, and UMODL1 were significantly (false discovery rate<0.05) associated with CKD by the GWAS. The relation of these five SNPs and of an additional 22 SNPs at these loci to CKD was examined in subject panel B, revealing that rs9846911 at 3q28 was significantly associated with CKD in all individuals and that rs2074381 and rs2074380 in ALPK1 were associated with CKD in individuals with diabetes mellitus. These three SNPs were further examined in subject panel C, revealing that rs2074381 and rs2074380 were significantly associated with CKD. For subject panels B and C combined, rs9846911 was significantly associated with CKD in all individuals and rs2074381 and rs2074380 were associated with CKD in diabetic individuals.
Chromosome 3q28 may be a susceptibility locus for CKD in Japanese individuals, and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes mellitus.
尽管全基因组关联研究（GWAS）已经在白种人和非裔美国人中发现了几个与慢性肾脏病（CKD）易感性相关的基因，但亚洲人群中导致 CKD 易感性的基因仍有待确定。我们进行了一项 GWAS，以确定导致日本个体发生 CKD 的遗传变异。
研究纳入了来自三个独立研究对象组的 3851 名日本个体。对象组 A、B 和 C 分别包含 252、910 和 190 名 CKD 患者以及 249、838 和 1412 名对照。在对象组 A 中进行了 CKD 的 GWAS。
在 GWAS 中，染色体 3q28 上的 5 个单核苷酸多态性（SNP）——ALPK1、FAM78B 和 UMODL1——与 CKD 显著相关（假发现率<0.05）。在对象组 B 中进一步检测了这 5 个 SNP 以及这些基因座上的另外 22 个 SNP 与 CKD 的关系，结果显示 3q28 上的 rs9846911 与所有个体的 CKD 显著相关，而 ALPK1 上的 rs2074381 和 rs2074380 与糖尿病患者的 CKD 相关。在对象组 C 中进一步检测了这 3 个 SNP，结果显示 rs2074381 和 rs2074380 与 CKD 显著相关。对于对象组 B 和 C 的合并分析，rs9846911 与所有个体的 CKD 显著相关，而 rs2074381 和 rs2074380 与糖尿病患者的 CKD 相关。
染色体 3q28 可能是日本人群 CKD 的易感位点，ALPK1 可能是糖尿病患者 CKD 的易感基因。
