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.

Guerini, F., Cagliani, R., Forni, D., Agliardi, C., Caputo, D., Cassinotti, A., et al. (2012). A Functional Variant in ERAP1 Predisposes to Multiple Sclerosis. PLOS ONE, 7(1) [10.1371/journal.pone.0029931].

A Functional Variant in ERAP1 Predisposes to Multiple Sclerosis

Sironi M
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.
Articolo in rivista - Articolo scientifico
Adult; Aminopeptidases; Crohn Disease; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Meta-Analysis as Topic; Multiple Sclerosis, Relapsing-Remitting; Polymorphism, Single Nucleotide
English
2012
7
1
e29931
open
Guerini, F., Cagliani, R., Forni, D., Agliardi, C., Caputo, D., Cassinotti, A., et al. (2012). A Functional Variant in ERAP1 Predisposes to Multiple Sclerosis. PLOS ONE, 7(1) [10.1371/journal.pone.0029931].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/514921
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