Zhou Junyi, Zhang Zhijian, Zhou Kezhi, Zhou Leting, Xue Jing, Liu Bin, Zhang Xiran, Cai Ting, Huang Biao, Zhang Yi, Hu Zhigang, Wang Liang, Liu Xiaobin
Department of Nephrology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, P.R. China.
College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, P.R. China.
PLoS One. 2025 Aug 22;20(8):e0328234. doi: 10.1371/journal.pone.0328234. eCollection 2025.
Primary membranous nephropathy is a widely recognized autoimmune disease associated with podocyte antigens; the most important autoantigen is PLA2R1. PLA2R1 and HLA-DQA1 play important roles in the production of pathogenic antibodies. The purpose of this study was to observe the relationship between gene polymorphisms and primary membranous nephropathy and explore the clinical functional clues of PLA2R1 and HLA-DQA1 genes affecting treatment responsiveness.
The study enrolled 89 patients with primary membranous nephropathy and 91 healthy people as a control. Single-nucleotide polymorphism loci (seven on PLA2R1 and two on HLA-DQA1) were identified using the PCR-Sanger technique. The patients were followed up until the 12th month, and relevant clinical data were collected. The relationship between these single-nucleotide polymorphism loci and primary membranous nephropathy remission was analyzed.
Genotypic and allelic frequency distributions for six single-nucleotide polymorphisms within PLA2R1 (rs4664308, rs3792189, rs3792192, rs1870102, rs17831251, and rs35771982) and one in HLA-DQA1 (rs2187668) were associated with morbidity of primary membranous nephropathy. Single-nucleotide polymorphisms rs1870102, rs17831251, and rs2187668 were statistically significant in the genetic model analysis. The odds ratio for primary membranous nephropathy in patients carrying rs2187668 GG and rs1870102 AA was 52.875. We found that PLA2R1 single-nucleotide polymorphism rs36771982 was related to proteinuria remission at the 12th month, and found in further analysis that PLA2R1 single-nucleotide polymorphisms rs3792189, rs3792192, rs17831251, and rs35771982 were related to treatment response in the RTX group.
In this study, we found several PLA2R1 and HLA-DQA1 single-nucleotide polymorphism loci associated with primary membranous nephropathy morbidity and that some PLA2R1 single-nucleotide polymorphism loci were related to the treatment response of patients with primary membranous nephropathy.
原发性膜性肾病是一种广泛认可的与足细胞抗原相关的自身免疫性疾病；最重要的自身抗原是PLA2R1。PLA2R1和HLA - DQA1在致病性抗体的产生中起重要作用。本研究的目的是观察基因多态性与原发性膜性肾病之间的关系，并探索PLA2R1和HLA - DQA1基因影响治疗反应性的临床功能线索。
本研究纳入89例原发性膜性肾病患者和91例健康人作为对照。采用PCR - Sanger技术鉴定单核苷酸多态性位点（PLA2R1上7个，HLA - DQA1上2个）。对患者进行随访至第12个月，并收集相关临床资料。分析这些单核苷酸多态性位点与原发性膜性肾病缓解之间的关系。
PLA2R1内6个单核苷酸多态性（rs4664308、rs3792189、rs3792192、rs1870102、rs17831251和rs35771982）以及HLA - DQA1内1个单核苷酸多态性（rs2187668）的基因型和等位基因频率分布与原发性膜性肾病的发病相关。单核苷酸多态性rs1870102、rs17831251和rs2187668在遗传模型分析中具有统计学意义。携带rs2187668 GG和rs1870102 AA的患者发生原发性膜性肾病的比值比为52.875。我们发现PLA2R1单核苷酸多态性rs36771982与第12个月时蛋白尿缓解相关，进一步分析发现PLA2R1单核苷酸多态性rs3792189、rs3792192、rs17831251和rs35771982与RTX组的治疗反应相关。
在本研究中，我们发现了几个与原发性膜性肾病发病相关的PLA2R1和HLA - DQA1单核苷酸多态性位点，并且一些PLA2R1单核苷酸多态性位点与原发性膜性肾病患者的治疗反应相关。
