The associations of single nucleotide polymorphisms (SNPs) in PLA2R1 and HLA-DQA1, as well as HLA-DRB1*15:01-DQB1*06:02 haplotype with idiopathic membranous nephropathy (IMN) is well known.
The pooled odds ratios (ORs) regarding the association between the HLA-DQA1rs2187668 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].
This study validated the association of these HLA-DQA1 and PLA2R1 SNPs with IMN in a Spanish cohort and its increased risk when combining both risk genotypes.
Recent studies have demonstrated that alleles at single nucleotide polymorphisms (SNPs) rs2187668 and rs4664308 within genes HLA-DQA1 and PLA2R1, respectively, had a significant impact on the susceptibility to idiopathic membranous nephropathy (IMN).
Our recent genome-wide association study showed that genetic variants in an HLA-DQA1 and phospholipase A2 receptor (PLA2R1) allele associate most significantly with biopsy-proven iMN, suggesting that rare genetic variants within the coding region of the PLA2R1 gene may contribute to antibody formation.
A genome-wide association study has provided further evidence for a highly significant association between PLA2R1 and HLA-DQA1 loci and idiopathic membranous nephropathy in patients of white ancestry.
In African Americans, much of the risk for end-stage nondiabetic kidney disease is explained by common variants in the MYH9/APOL1 locus, and in individuals of European descent, variants in HLA-DQA1 and PLA(2)R1 implicate most of the risk for idiopathic membranous nephropathy.
The incidence of DQA1*0501 was raised in both Greek (96% vs. 66%, OR 9.7, chi 2 6.9, P = 0.009) and British IMN (85% vs. 45%, OR 7.4, chi 2 20, P = 0.00007) patients.
Furthermore, patients with PLA2R-associated IMN had significantly higher age (with vs without, 54.31 ± 14.03 vs 46.67 ± 13.30 years old; P = .04), proteinuria (4.32 ± 1.84 vs 3.29 ± 1.90 g/d, P = .039), and serum albumin (25.33 ± 9.60 vs 31.38 ± 9.52 g/L, P = .019), but had lower serum immunoglobulin G (6.83 ± 2.89 vs 8.72 ± 2.95 g/L, P = .016) and erythrocyte sedimentation rate (47.31 ± 32.11 vs 26.33 ± 27.94, P = .013), when compared to IMN patients without PLA2R.
The titer of anti-PLA2R antibody was significantly correlated with both TUpro and serum Alb levels of pre- and post-therapeutic values in IMN (P<0.05), but did not have a relationship with Ccr (P>0.05).
Significant differences in systolic blood pressure, serum Cystatin C, serum albumin and estimated glomerular filtration rate (eGFR) were found between the antibody-positive and antibody-negative groups of IMN patients.
Statistical analyses indicated that there were positive correlations between uPLA<sub>2</sub>R-Ab and gPLA<sub>2</sub>R, sPLA<sub>2</sub>R-Ab or urinary protein and negative correlations between uPLA<sub>2</sub>R-Ab and serum albumin in patients with IMN.
Furthermore, CD14<sup>+</sup>CD163<sup>+</sup>CD206<sup>+</sup> M2-like cell counts in the patients with incipient IMN were also positively related with 24 h urinary albumin levels and the values of serum M-type phospholipase A2 receptor (PLA2R).
UAGT levels were correlated negatively with serum albumin (r = - 0.393, p = 0.006) and estimated glomerular filtration rate (eGFR) (r = - 0.352, p = 0.014) and positively with 24-h proteinuria (r = 0.614, p < 0.001) in iMN patients but not in MCD patients.
The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41).