title: Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population.
abstract: Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.
authors.affiliation: Servicio de Inmunología, IBiS, H.U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Conde-Jaldón
authors.affiliation: Servicio de Inmunología, IBiS, H.U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Montes-Cano
authors.affiliation: Servicio de Inmunología, IBiS, H.U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: José Raul
authors.initials: JR
authors.lastname: García-Lozano
authors.affiliation: Servicio de Inmunología, IBiS, H.U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ortiz-Fernández
authors.affiliation: Servicio de Medicina Interna, H. Clínico San Cecilio, Granada, Spain.
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.affiliation: Servicio de Medicina Interna, H. U. Virgen del Rocío, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: González-León
authors.affiliation: Servicio de Enfermedades Autoinmunes, H. Clinic, Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.affiliation: Servicio de Reumatología, CHU A Coruña, Spain.
authors.forename: Genaro
authors.initials: G
authors.lastname: Graña-Gil
authors.affiliation: Servicio de Reumatología, H. de Valme, Sevilla, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sánchez-Bursón
authors.affiliation: Servicio de Reumatología, H. Marques de Valdecilla, Santander, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: González-Gay
authors.affiliation: Servicio de Medicina Interna, H. Torrecárdenas, Almería, Spain.
authors.forename: Ana Celia
authors.initials: AC
authors.lastname: Barnosi-Marín
authors.affiliation: Servicio de Medicina Interna, H. Vall d'Hebron, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Solans
authors.affiliation: Servicio de Medicina Interna, H. Virgen del Camino, Pamplona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fanlo
authors.affiliation: Medicina Interna Unitat de Malalties Autoimmunes i Sistèmiques Hospital Universitari Mútua Terrassa, Barcelona, Spain.
authors.forename: Mónica Rodríguez
authors.initials: MR
authors.lastname: Carballeira
authors.affiliation: Servicio de Medicina Interna, H. Carlos Haya, Málaga, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Camps
authors.affiliation: Servicio de Reumatología, H. de la Princesa, Madrid, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Servicio de Inmunología, IBiS, H.U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: María Francisca
authors.initials: MF
authors.lastname: González-Escribano
mesh_terms: D000328:Adult; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D001528:Behcet Syndrome / Q000453:epidemiology* / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D015778:Minor Histocompatibility Antigens; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013030:Spain / Q000453:epidemiology
chemical_list: D015235:HLA-B Antigens; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human