Association between PLA2R1 rs4664308 and susceptibility to idiopathic membranous nephropathy

Abstract

Previous studies have evaluated the association between the phospholipase A2 m-type receptor ( PLA2R1) rs4664308 polymorphism and the risk of idiopathic membranous nephropathy (IMN), but the results need to be integrated. We hypothesized that the PLA2R1 rs4664308 polymorphism is associated with IMN risk in different ethnicities and assessed this hypothesis by using meta-analysis and case-control studies. A literature searches on PLA2R1 rs4664308 and IMN risk was conducted using the EMBASE, PubMed, Cochrane Library, and Chinese Medical Databases. The relationship between PLA2R1 rs4664308 and IMN risk was evaluated in 5 genetic models, namely, allelic (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) models. Subgroup analysis was conducted by ethnicity on Asian and non-Asian populations. Eight sets of data from 6 articles met study objectives were selected and 6797 subjects (IMN: 2324 Controls: 4,473) were included. Heterogeneity was found in the DG, HMG, and HTG models but not in the AG or RG models. The minor allele(G) of PLA2R1 rs4664308 showed a significant negative correlation with IMN risk in all genetic random models: odds ratio of AG: 0.44(0.37-0.51), RG: 0.35(0.29-0.42), DG: 0.38(0.31-0.48), HMG: 0.26(0.19-0.37), and HTG: 0.61(0.48-0.77; P < .00001), and Asians and non-Asians showed the same effect of PLA2R1 rs4664308 on IMN risk. Analysis of Asians and non-Asians revealed no publication bias in any of the 5 genetic models. The minor allele of PLA2R1 rs4664308 has a protective activity against IMN in Asians and non-Asians. It provided new insights into potential curative and preventative treatments for IMN.

Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression

“…In fact, over the past decade several studies focused on PLA2R and HLA-DQA1 gene polymorphisms, though with inconsistent findings. Although, previous meta-analyses were published in 2018 for the HLA-DQA1 rs2187668 SNP, 8 and in 2020 for the PLA2R rs4664308 SNP, 6 , 7 the literature search cut-off time in our study was fresher. Besides, to the best of our knowledge, this study was the first to summarize published results on PMN risk conferred by the following PLA2R SNPs, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, and rs2715918.…”

“…Three previous meta-analyses assessing PMN genetic risk; 2 for the PLA2R rs4664308 polymorphism (SNP) in 2020 6 , 7 ; and 1 for the HLA-DQA1 rs2187668 SNP in 2018 8 ; have been already published. Nevertheless, these aforementioned meta-analyses included only a few studies (7–11) and revealed a high level of between-study heterogeneity with inconsistent results.…”

“…Nevertheless, these aforementioned meta-analyses included only a few studies (7–11) and revealed a high level of between-study heterogeneity with inconsistent results. 6 , 8 Moreover, subgroup analyses by ethnicity failed to explain the heterogeneity and the between-studies inconsistency. 6 , 8 Furthermore, these previous meta-analyses did not perform extensive meta-regressions in order to investigate the aforementioned between-studies heterogeneity.…”

“… 6 , 8 Moreover, subgroup analyses by ethnicity failed to explain the heterogeneity and the between-studies inconsistency. 6 , 8 Furthermore, these previous meta-analyses did not perform extensive meta-regressions in order to investigate the aforementioned between-studies heterogeneity. Therefore, including more studies and a deeper investigation of the sources of heterogeneity are needed.…”

“…Therefore, including more studies and a deeper investigation of the sources of heterogeneity are needed. In addition, the risk conferred by the PLA2R rs4664308 SNP (OR = 2.27) 6 , 7 and the HLA-DQA1 rs218668 SNP (OR = 3.34) 8 represents only a small part of the genetic component predisposing to PMN. Indeed, other SNPs could contribute to PMN susceptibility, and thus require further investigation to better characterize the predisposing genetic landscape.…”