Background: Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated. Objectives: The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions. Design: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses. Data sources and methods: An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668. Results: Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all P -values <.001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, P <.001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251–4.748]) than in Asians (OR [95% CI] = 2.537 [1.94–3.318], P =.007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease. Conclusion: This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP. Registration: This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729 Plain language summary: Genetic factors in primary membranous nephritis Why was the study done? Primary membranous nephritis (PMN) is the most common etiology of adult-onset nephrotic syndrome. Understanding risk factors, particularly genetic ones, would provide a better understanding of its pathophysiological mechanisms in order to prevent and treat patients more effectively. What did the researchers do? The research team summarized published data on genetic factors associated with PMN including phospholipase A2 receptor (PLA2R) and HLA-DQA1 genes. What did the researchers find? The total number of included studies was 27. Nine out of ten genetic factors were found to be associated with PMN risk. Moreover, we noted significant interaction between PLA2R and HLA-DQA1 in potentializing PMN risk. Nevertheless, there was a significant between-studies heterogeneity which was found to be explained in part by disease severity. What do the findings mean? This study has identified some important some genetic factors associated with PMN together with confounding factors that could influence the aforementioned association. [ABSTRACT FROM AUTHOR]