Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis

Sci Rep. 2020 Aug 4;10(1):13119. doi: 10.1038/s41598-020-70009-x.

Abstract

Although many studies investigated the associations between single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) gene and susceptibility to idiopathic membranous nephropathy (IMN), some showed inconsistent results. Here, we conducted a meta-analysis examining the associations between PLA2R1 SNPs and IMN susceptibility after systematic searches in the PubMed and Web of Science databases. Our meta-analysis for rs4664308 A>G including 2,542 IMN patients and 4,396 controls in seven studies showed a significant association between the G allele and a lower risk of IMN, as determined using an allelic model (odds ratio, 0.45; 95% confidence interval [0.41-0.50]), an additive model (for GG vs. AA: 0.26; [0.21-0.33]; for AG vs. AA: 0.40; [0.36-0.45]), a dominant model (0.37; [0.34-0.42]) and a recessive model (0.38; [0.31-0.48]). Our meta-analysis also suggested associations between rs3828323, rs35771982, rs3749117 and rs3749119 and IMN susceptibility although high heterogeneities and/or publication biases were observed. We did not study in our meta-analysis, but other studies indicated that high-risk genotype combinations of rs2187668 in the human leucocyte antigen-DQ a-chain 1 gene and rs4664308 in the PLA2R1 gene had even stronger associations and could affect the formation of anti-PLA2R1 antibodies, suggesting these SNPs could be novel therapeutic targets.

Publication types

  • Meta-Analysis

MeSH terms

  • Genetic Predisposition to Disease / genetics*
  • Glomerulonephritis, Membranous / genetics*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Receptors, Phospholipase A2 / genetics*

Substances

  • PLA2R1 protein, human
  • Receptors, Phospholipase A2