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 (p(meta) = 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.

A functional variant in ERAP1 predisposes to multiple sclerosis / F.R. Guerini, R. Cagliani, D. Forni, C. Agliardi, D. Caputo, A. Cassinotti, D. Galimberti, C. Fenoglio, M. Biasin, R. Asselta, E. Scarpini, G.P. Comi, N. Bresolin, M.S. Clerici, M. Sironi. - In: PLOS ONE. - ISSN 1932-6203. - 7:1(2012), pp. e29931.e29931.1-e29931.e29931.4.

A functional variant in ERAP1 predisposes to multiple sclerosis

D. Galimberti;C. Fenoglio;M. Biasin;R. Asselta;E. Scarpini;G.P. Comi;N. Bresolin;M.S. Clerici;
2012

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 (p(meta) = 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.
Settore MED/04 - Patologia Generale
Settore BIO/13 - Biologia Applicata
Settore BIO/11 - Biologia Molecolare
2012
Article (author)
File in questo prodotto:
File Dimensione Formato  
journal.pone.0029931.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 74.3 kB
Formato Adobe PDF
74.3 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/191990
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 45
  • ???jsp.display-item.citation.isi??? 45
social impact