The Presence of Risk and Protective HLA-DQ Haplotype Combinations and PLA2R1 Risk SNP in Hungarian Patients with...

Area of Science:

• Nephrology
• Immunogenetics
• Molecular Biology

Background:

• The genetic basis of primary membranous nephropathy (pMN) remains incompletely understood.
• Specific HLA-DQ serotypes and phospholipase A2 receptor 1 (PLA2R1) gene single-nucleotide polymorphisms (SNPs) are known risk factors for pMN.
• Antigen presentation involves HLA-DQA/DQB dimers, suggesting HLA-DQ haplotype combinations may influence MN evolution.

Purpose of the Study:

• To investigate the association between HLA-DQ haplotype combinations, PLA2R1 gene variants, and the risk of developing primary and secondary membranous nephropathy (MN).
• To identify specific HLA-DQ haplotypes that confer risk or protection against MN.
• To clarify the role of PLA2R1 in primary versus secondary MN.

Main Methods:

• Genotyping of HLA-DQ haplotype combinations and the PLA2R1 risk variant (rs4664308) in 67 MN patients (52 pMN, 15 sMN) and 77 controls.
• Utilizing a scoring system based on PLA2R1 risk alleles to assess risk and identify protective HLA-DQ haplotypes.
• Statistical analysis to compare frequencies between patient groups and controls.

Main Results:

• The HLA-DQ 2.5 serotype was significantly more frequent in both pMN and sMN patients compared to controls.
• The pMN group showed a higher frequency of the PLA2R1 risk allele than sMN patients and controls.
• HLA-DQ 2.5 was associated with the highest risk for pMN, while HLA-DQ 7.5 and 6.2 appeared protective.

Conclusions:

• HLA-DQ 2.5 is strongly associated with an increased risk for both primary and secondary membranous nephropathy, potentially due to reduced antigen specificity and induction of autoimmune responses.
• The PLA2R1 gene variant contributes to the development of pMN but not sMN.
• Specific HLA-DQ haplotypes play a significant role in the pathogenesis of membranous nephropathy.