Interaction between PLA2R1 and HLA-DQA1 variants contributes to the increased genetic susceptibility to membranous nephropathy in Western China

Aim: Recent studies showed that single nucleotide polymorphisms (SNP) within the phospholipase A2 receptor (PLA2R1) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) genes were associated with the susceptibility to patients with primary membranous nephropathy (PMN). However, the results of previous research have not been always consistent. Methods: We performed a case–control study including 314 patients with PMN and 354 healthy subjects in Western China. Eight SNP in PLA2R1 and one SNP in HLA -DQA1 were genotyped and association between PLA2R1 and HLA-DQA1 was investigated. One hundred and twenty patients were detected anti-PLA2R antibodies to analyze the association between genotype and anti-PLA2R antibody. Results: We found A allele of rs2715918 (odds ratio (OR) = 1.66, corrected P values (Pc) = 7.9 × 10 ⁻³ ), A allele of rs4665143 (OR = 1.76, Pc = 2.7 × 10 ⁻⁶ ) and A allele of rs2187668 (OR = 3.29, Pc = 8.0 × 10 ⁻¹¹ ) were associated with PMN. Susceptibility of PMN was significantly increased with rs2715918 in dominant model (OR = 1.624, Pc = 5.0 × 10 ₋₂ ), rs4665143 in recessive model (OR = 2.134, Pc = 1.4 × 10 ⁻⁴ ) and rs2187668 in dominant model (OR = 3.961, Pc = 4.1 × 10 ⁻¹¹ ). The haplotype ATAC of rs2715918, rs6757188, rs4665143, rs3749119 was associated with the high risk of PMN (OR = 1.453, P = 3.0 × 10 ⁻⁴ ). Interaction of rs2715918 GA/AA, rs4665143 GA/AA and rs2187668 GA/AA could significantly increase the 10.61-fold higher risk for the development of PMN (OR = 10.61, P = 4.0 × 10 ⁻¹⁰ ). Patients who carried with risk genotypes for both HLA-DQA1 and PLA2R1 (87.8%) had antibodies positivity. However, patients who carried low-risk genotypes (41.6%) had antibodies positivity (P = 0.001). Conclusion: There are some differences in PLA2R1 distributions in PMN patients between previous literature and our study. Our results showed that interactions between PLA2R1 and HLA-DQA1 alleles increased genetic susceptibility to PMN in Western China.