Journal Article

HLA-DQ and HLA-DRB1 alleles associated with Henoch-Schönlein purpura nephritis in Finnish pediatric population: a genome-wide association study

Nuutinen Matti, Ritari Jarmo, Ylinen Elisa, Koskela Mikael, Kaija-Leena, Kolho, Nihtilä Julia, Jahnukainen Timo

2021

Overview

BackgroundThe pathophysiology of Henoch-Schönlein purpura (HSP) is still unclear, but several findings suggest that genetic factors may influence disease susceptibility. We aimed to perform a genome-wide association study (GWAS) in pediatric HSP patients with an emphasis on severe HSP nephritis.MethodsThe study included 46 HSP patients, 42 of whom had undergone kidney biopsy. Forty-nine pediatric patients with an inflammatory bowel disease (IBD) served as an autoimmune disease control group while Finnish bone marrow and blood donors represented the general reference population (n = 18,757). GWAS was performed for HSP and IBD samples in a case-control manner against the reference population. The analysis also included imputation of human leukocyte antigen (HLA) alleles.ResultsGWAS analysis in HSP revealed several polymorphisms from the HLA region that surpassed the genome-wide significance level. Three HLA class II alleles were also significantly more frequent in HSP than in the reference population: DQA1*01:01, DQB1*05:01, and DRB1*01:01. Haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 occurred in 43.5% of HSP patients, whereas its frequency was 8.2% in IBD patients and 15.0% in the reference population. HSP patients with this haplotype showed similar baseline clinical findings and outcome as HSP patients negative for the haplotype. In IBD patients, no polymorphism or HLA allele appeared significant at the genome-wide level.ConclusionsOur results suggest that haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 is associated with susceptibility to HSP, but not with the severity of the kidney involvement. These HLA associations did not occur in IBD patients, suggesting that they are specific to HSP and not related to susceptibility to autoimmune diseases in general.

• Publisher: Springer Nature B.V
• Subject: Alleles / Autoimmune diseases / Biopsy / Blood donors / Bone marrow / Bone marrow transplantation / Crohn's disease / Disease / Disease control / DQA1 protein / Drb1 protein / Gene polymorphism / Genetic factors / Genome-wide association studies / Genomes / Haplotypes / Histocompatibility antigen HLA / Inflammatory bowel disease / Inflammatory bowel diseases / Kidneys / Nephritis / Patients / Pediatrics / Population / Population genetics / Population studies / Purpura / Schonlein-Henoch purpura