rs112396255 (HLA-DRB1): IgA Vasculitis Risk Variant
Key takeaways
- The HLA haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 was found in 43.5% of Finnish children with HSP versus 15% in the general population
- This HLA association appears specific to HSP (IgA vasculitis) and was not seen in inflammatory bowel disease patients
- The haplotype was linked to HSP susceptibility but not to the severity of kidney involvement
- The variant affects expression of nearby HLA genes across multiple tissues, including skeletal muscle and lung
- Evidence is from a small study of 46 patients and should be considered preliminary
Key takeaways
- The HLA haplotype DQA101:01/DQB105:01/DRB1*01:01 was found in 43.5% of Finnish children with HSP versus 15% in the general population
- This HLA association appears specific to HSP (IgA vasculitis) and was not seen in inflammatory bowel disease patients
- The haplotype was linked to HSP susceptibility but not to the severity of kidney involvement
- The variant affects expression of nearby HLA genes across multiple tissues, including skeletal muscle and lung
- Evidence is from a small study of 46 patients and should be considered preliminary
What the research says A genome-wide association study (GWAS) in Finnish pediatric patients identified several polymorphisms in the HLA class II locus (HLA-DRB1 - HLA-DQA1 region) reaching genome-wide significance in Henoch-Schonlein purpura (HSP, also known as IgA vasculitis - a condition in which small blood vessels become inflamed, causing a purplish rash and sometimes kidney damage, predominantly in children). Three alleles at this locus were each significantly more frequent in HSP patients than in the general Finnish population: DQA101:01, DQB105:01, and DRB101:01. The combined haplotype (a set of alleles inherited together on the same chromosome) DQA101:01/DQB105:01/DRB101:01 was present in 43.5% of HSP patients, compared to 15.0% in the general Finnish population and 8.2% in pediatric inflammatory bowel disease patients who served as an autoimmune disease comparison group.
Reported associations
- Henoch-Schonlein purpura susceptibility: The haplotype DQA101:01/DQB105:01/DRB1*01:01 was found in 43.5% of 46 HSP patients versus 15.0% of 18,757 Finnish population controls, with several HLA region polymorphisms reaching genome-wide significance in a pediatric GWAS.
- HSP kidney involvement severity: The associated haplotype showed no link to differences in kidney disease severity; HSP patients with and without this haplotype had similar baseline clinical findings and long-term kidney outcomes.
- Inflammatory bowel disease (IBD): No polymorphism or HLA allele at this locus reached genome-wide significance in the 49 IBD patients studied, suggesting the observed HSP associations are disease-specific rather than general markers of autoimmune susceptibility.
Evidence quality This evidence comes from a single GWAS in a Finnish pediatric cohort comprising 46 HSP cases, 49 IBD autoimmune controls, and 18,757 population reference donors. Multiple polymorphisms at the HLA class II locus surpassed genome-wide significance in HSP, and imputed HLA alleles showed significant enrichment for the DQA101:01/DQB105:01/DRB1*01:01 haplotype. The primary limitation is the small case sample size, which reduces statistical power for subgroup analyses such as kidney involvement severity. The IBD comparison group provides useful context for disease specificity, since no signal appeared in that group. Independent replication in larger, ethnically diverse cohorts is needed before firm conclusions can be drawn. No conflicting findings from other studies were provided.
Tissue-specific expression effects
- HLA-DQB1: The alternate allele is associated with increased expression in skeletal muscle GTEx Portal
- HLA-DRB6: The alternate allele is associated with reduced expression across multiple tissues including esophagus (both the muscularis and mucosal layers), lung, subcutaneous adipose tissue, skeletal muscle, and thyroid GTEx Portal
- HLA-DQB2: The alternate allele is associated with reduced expression in tibial nerve GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is Henoch-Schonlein purpura (HSP)?
Henoch-Schonlein purpura, also called IgA vasculitis, is an inflammatory condition in which small blood vessels become inflamed. It typically causes a purplish rash, joint pain, and sometimes kidney involvement, and it mostly affects children.
What HLA genes are associated with rs112396255?
This variant sits in the HLA class II region near HLA-DRB1 and HLA-DQA1, which encode proteins on immune cells that help recognize foreign substances. The associated risk haplotype includes alleles DQA1*01:01, DQB1*05:01, and DRB1*01:01.
Is rs112396255 linked to kidney disease severity in HSP?
No. In the Finnish pediatric GWAS, the associated haplotype was linked to susceptibility to HSP but not to the severity of kidney involvement. Patients with and without the haplotype had similar clinical findings and kidney outcomes.
How strong is the evidence linking rs112396255 to HSP?
The evidence comes from a single GWAS of 46 pediatric HSP patients, which is a small sample. The variant reached genome-wide significance within the HLA region, but independent replication in larger cohorts is needed before strong conclusions can be drawn.
Does rs112396255 affect how HLA genes are expressed in the body?
GTEx data show the variant is associated with increased HLA-DQB1 expression in skeletal muscle, reduced HLA-DRB6 expression across several tissues including lung, esophagus, and thyroid, and reduced HLA-DQB2 expression in tibial nerve. These are tissue-level expression effects and their clinical significance is not established.