Kaga Hajime, Komatsuda Atsushi, Omokawa Ayumi, Okuyama Shin, Mori Kensuke, Wakui Hideki, Takahashi Naoto
Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, Akita, 010-8543, Japan.
Department of Life Science, Akita University Graduate School of Engineering Science, 1-1 Tegatagakuen-machi, Akita City, Akita, 010-8502, Japan.
Clin Exp Nephrol. 2018 Apr;22(2):275-282. doi: 10.1007/s10157-017-1471-0. Epub 2017 Aug 28.
Several recent studies in patients with idiopathic membranous nephropathy (iMN) from Western and Asian counties showed that some single nucleotide polymorphisms (SNPs) within the PLA2R1 and HLA-DQA1 genes are significantly associated with iMN. However, there is only 1 report on analysis of PLA2R1 and HLA regions in Japanese patients with iMN.
A total of 58 patients with iMN, 26 patients with secondary MN (sMN), and 50 patients with other diseases were enrolled. All patients were Japanese. We selected 6 SNPs within PLA2R1 and 1 SNP within HLA-DQA1, which were significantly associated with iMN in reported white European cohorts, and sequenced these exons using genomic DNA prepared from peripheral mononuclear cells from each patient. We then analyzed differences in PLA2R1 and HLA-DQA1 sequence variants among the 3 groups.
Genotypic and allelic frequency distributions for 3 out of 6 SNPs within PLA2R1, rs3749117, rs35771982, and rs2715918 were significantly different between the iMN and control groups. Allelic frequency distributions for SNP rs2187668 within HLA-DQA1 were significantly different between the iMN and control groups. There were no correlations between PLA2R1 and HLA-DQA1 sequence variants and clinical parameters in patients with iMN. There were no significant differences in genotypic or allelic frequency distributions for examined SNPs between the sMN and control groups.
There are some differences in PLA2R1 SNP distributions between previously reported cohorts from other countries and our Japanese cohort of patients with iMN, while there is a significant association between SNP rs35771982 and iMN in most of reported cohorts.
近期来自西方和亚洲国家的多项针对特发性膜性肾病（iMN）患者的研究表明，PLA2R1和HLA - DQA1基因内的一些单核苷酸多态性（SNP）与iMN显著相关。然而，关于日本iMN患者PLA2R1和HLA区域分析的报告仅有1篇。
共纳入58例iMN患者、26例继发性膜性肾病（sMN）患者和50例其他疾病患者。所有患者均为日本人。我们选择了PLA2R1基因内的6个SNP和HLA - DQA1基因内1个与已报道的白种欧洲人群队列中iMN显著相关的SNP，并使用从每位患者外周血单个核细胞制备的基因组DNA对这些外显子进行测序。然后我们分析了这3组之间PLA2R1和HLA - DQA1序列变异的差异。
PLA2R1基因内6个SNP中的3个，即rs3749117、rs35771982和rs2715918，其基因型和等位基因频率分布在iMN组和对照组之间存在显著差异。HLA - DQA1基因内SNP rs2187668的等位基因频率分布在iMN组和对照组之间存在显著差异。iMN患者中PLA2R1和HLA - DQA1序列变异与临床参数之间无相关性。sMN组和对照组之间所检测SNP的基因型或等位基因频率分布无显著差异。
在先前报道的其他国家队列与我们的日本iMN患者队列之间，PLA2R1 SNP分布存在一些差异，而在大多数已报道队列中，SNP rs35771982与iMN之间存在显著关联。
