HLA-DQA1 and PLA2R1 Polymorphisms and Risk of Idiopathic Membranous Nephropathy
- 1 February 2014
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Clinical Journal of the American Society of Nephrology
- Vol. 9 (2), 335-343
- https://doi.org/10.2215/cjn.05310513
Abstract
Background and objectives 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. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease. Design, settings, participants, & measurements A Spanish cohort of 89 IMN patients and 286 matched controls without nephropathy was recruited between October of 2009 and July of 2012. Case-control studies for SNPs within HLA-DQA1 (rs2187668) and PLA2R1 (rs4664308) genes and CNVs for FCGR3A and FCGR3B genes were performed. The contribution of these polymorphisms to predict clinical outcome and renal function decline was analyzed. Results 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. No significant association was found between FCGR3 CNVs and IMN. These results revealed that HLA-DQA1 and PLA2R1 genotype combination adjusted for baseline proteinuria strongly predicted response to immunosuppressive therapy. HLA-DQA1 genotype adjusted for proteinuria was also linked with renal function decline. Conclusion This study confirms that HLA-DQA1 and PLA2R1 genotypes are risk factors for IMN, whereas no association was identified for FCGR3 CNVs. This study provides, for the first time, evidence of the contribution of these HLA-DQA1 and PLA2R1 polymorphisms in predicting IMN response to immunosuppressors and disease progression. Future studies are needed to validate and identify prognostic markers.This publication has 45 references indexed in Scilit:
- Identification and Characterization of a New Autoimmune Protein in Membranous Nephropathy by Immunoscreening of a Renal cDNA LibraryPLOS ONE, 2012
- Antiphospholipase A2 Receptor Antibody Titer and Subclass in Idiopathic Membranous NephropathyJournal of the American Society of Nephrology, 2012
- Prognostic Value of Risk Score and Urinary Markers in Idiopathic Membranous NephropathyClinical Journal of the American Society of Nephrology, 2012
- Pathogenesis of membranous nephropathy: recent advances and future challengesNature Reviews Nephrology, 2012
- Meta-analysis confirms a role for deletion in FCGR3B in autoimmune phenotypesHuman Molecular Genetics, 2012
- Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: Alfa-enolase and borderline antigensJournal of Proteomics, 2011
- Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous NephropathyJournal of the American Society of Nephrology, 2011
- New insights into membranous glomerulonephritis: from bench to bedside.Nephrology Dialysis Transplantation, 2011
- Risk HLA-DQA1 and PLA2R1 Alleles in Idiopathic Membranous NephropathyThe New England Journal of Medicine, 2011
- Single Nucleotide Polymorphisms in the Phospholipase A2 Receptor Gene Are Associated with Genetic Susceptibility to Idiopathic Membranous NephropathyNephron Clinical Practice, 2010