A Functional Variant in ERAP1 Predisposes to Multiple Sclerosis
Open Access
- 12 January 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (1), e29931
- https://doi.org/10.1371/journal.pone.0029931
Abstract
The ERAP1 gene encodes an aminopeptidase involved in antigen processing. A functional polymorphism in the gene (rs30187, Arg528Lys) associates with susceptibility to ankylosying spondylitis (AS), whereas a SNP in the interacting ERAP2 gene increases susceptibility to another inflammatory autoimmune disorder, Crohn's disease (CD). We analysed rs30187 in 572 Italian patients with CD and in 517 subjects suffering from multiple sclerosis (MS); for each cohort, an independent sex- and age-matched control group was genotyped. The frequency of the 528Arg allele was significantly higher in both disease cohorts compared to the respective control population (for CD, OR = 1.20 95%CI: 1.01–1.43, p = 0.036; for RRMS, OR = 1.26; 95%CI: 1.04–1.51, p = 0.01). Meta-analysis with the Wellcome Trust Cases Control Consortium GWAS data confirmed the association with MS (pmeta = 0.005), but not with CD. In AS, the rs30187 variant has a predisposing effect only in an HLA-B27 allelic background. It remains to be evaluated whether interaction between ERAP1 and distinct HLA class I alleles also affects the predisposition to MS, and explains the failure to provide definitive evidence for a role of rs30187 in CD. Results herein support the emerging concept that a subset of master-regulatory genes underlay the pathogenesis of autoimmunity.Keywords
This publication has 31 references indexed in Scilit:
- Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibilityNature Genetics, 2011
- Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47Nature Genetics, 2011
- Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility lociNature Genetics, 2010
- Unraveling the Genetics of AutoimmunityCell, 2010
- HLA-class I markers and multiple sclerosis susceptibility in the Italian populationGenes & Immunity, 2009
- Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility lociNature Genetics, 2009
- The quality control of MHC class I peptide loadingCurrent Opinion in Cell Biology, 2008
- Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's diseaseNature Genetics, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptidesin vivoand plays an important role in immunodominanceProceedings of the National Academy of Sciences, 2006