To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects.
Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ α-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study.
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.
The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients.
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.
We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence.