Association between the HLA-DQA1 rs2187668 polymorphism and risk of idiopathic membranous nephropathy

Abstract

Objective:Numerous studies have evaluated the association between the rs2187668 polymorphism in the human leucocyte antigen (HLA) complex class II HLA-DQ a-chain 1 (HLA-DQA1) gene and idiopathic membranous nephropathy (iMN) risk, which provided new insight into potential new targets for the treatment of iMN. However, this relationship remains inconclusive. Our aim was to evaluate the relationship between this polymorphism and iMN susceptibility by performing a meta-analysis.Methods:Articles were identified in the PubMed, Google Scholar, EMBASE, Cochran Library databases. Meta-analyses were performed for rs2187668 allele frequency, genotypes, and the association with iMN susceptibility. Subgroup analyses, publication bias and sensitivity analyses were also conducted.Results:11 eligible studies (3209 cases and 7358 controls) from 7 articles were included. Statistical analyses were carried out using Stata 12.0, combining data from all the relevant studies. The pooled odds ratios (ORs) regarding the association between the HLA-DQA1 rs2187668 polymorphism and iMN risk were statistically significant [A vs G: OR = 3.34, 95% confidence interval (CI) = 2.70–4.13; AA vs GA + GG: OR = 8.69, 95% CI = 6.64–11.36; GG vs GA + AA: OR = 0.25, 95% CI = 0.19–0.33;AA vs GG: OR = 12.61, 95% CI = 8.02–19.81; GA vs GG: OR = 3.45, 95% CI = 2.79–4.25].Conclusions:Our pooled analysis showed a significant association between rs2187668—(A) allele and iMN susceptibility, and the intervention of this mutation might bring new therapeutic strategy for iMN. However, further studies should be performed to confirm this finding.

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

“…Both rs2187668 alone and rs4664308 alone were associated with IMN susceptibility, as shown by the past 9 and the present meta-analysis. We have not studied SNPs in the HLA-DQA1 gene or interactions between the HLA-DQA1 and PLA2R1 genes in the present meta-analysis, but other researchers have reported that high-risk genotype combinations of both rs2187668 and rs4664308 have even stronger associations.…”

“…These results suggested that genetic variations of HLA-DQA1 and PLA2R1 proteins might facilitate auto-Ab formation against antigens at podocytes during the development of IMN. Since then, several studies have reported associations between HLA-DQA1 SNP rs2187668 and IMN susceptibility, and a recent meta-analysis indicated that the minor A allele was associated with IMN susceptibility, though some heterogeneities were observed 9 . As for PLA2R1 SNPs, not only rs4664308, but also other SNPs were reported to be associated with IMN susceptibility in numerous studies, although some studies showed inconsistent results.…”

“…Recently, several case–control studies have been performed to investigate the associations between SNPs in the genes encoding HLA-DQA1 and/or PLA2R1 and IMN susceptibility. In 2018, Bao et al performed a meta-analysis to confirm that HLA-DQA1 rs2187668 was associated with the risk of IMN 9 . However, a meta-analysis investigating the associations between SNPs in the PLA2R1 gene and IMN susceptibility has not yet been performed.…”

Association between PLA2R1 rs4664308 and susceptibility to idiopathic membranous nephropathy

“…However, studies have shown Asians are less likely to exhibit PLA2R1 genetic variations to increase IMN risk. [ 14 ] In 2014, a meta-analysis showed the presence of the PLA2R1 antibody could be used to diagnose IMN and suggested a serum PLA2R1 antibody test might be useful for detecting IMN. [ 33 ] In the same year, a new type of assay was developed to determine the presence of the PLA2R1 antibody in IMN.…”

“…Furthermore, the interaction between PLA2R1 and HLA is known to induce IMN. Bao et al [ 14 ] have concluded that the HLA alpha chain-1 ( HLA-DQA1 ) gene has a greater prevalence in Asians, Europeans, and Caucasians with IMN than in normal controls in a meta-analysis on the relation between HLA-DQA1 and IMN. Genome-wide association studies have found that PLA2R1 and HLA-DQA1 single nucleotide polymorphisms (SNPs) are high-risk to IMN, and the SNPs are interacted to induce IMN.…”