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Title: Genetic Analysis with the Immunochip Platform in Behçet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci.
Authors: Ortiz-Fernández, Lourdes
Carmona, Francisco-David
Montes-Cano, Marco-Antonio
García-Lozano, José-Raúl
Conde-Jaldón, Marta
Ortego-Centeno, Norberto
Castillo, María Jesús
Espinosa, Gerard
Graña-Gil, Genaro
Sánchez-Bursón, Juan
Juliá, María Rosa
Solans, Roser
Blanco, Ricardo
Barnosi-Marín, Ana-Celia
Gómez de la Torre, Ricardo
Fanlo, Patricia
Rodríguez-Carballeira, Mónica
Rodríguez-Rodríguez, Luis
Camps, Teresa
Castañeda, Santos
Alegre-Sancho, Juan-Jose
Martín, Javier
González-Escribano, María Francisca
metadata.dc.subject.mesh: Alleles
Behcet Syndrome
Case-Control Studies
Gene Frequency
Genetic Loci
Genetic Predisposition to Disease
HLA-A3 Antigen
HLA-B Antigens
HLA-B51 Antigen
Interleukin-12 Subunit p35
Logistic Models
Microarray Analysis
Models, Molecular
Receptors, Interleukin
Issue Date: 22-Aug-2016
Abstract: Behcet's disease (BD) is an immuno-mediated vasculitis in which knowledge of its etiology and genetic basis is limited. To improve the current knowledge, a genetic analysis performed with the Immunochip platform was carried out in a population from Spain. A discovery cohort comprising 278 BD cases and 1,517 unaffected controls were genotyped using the Immunochip platform. The validation step was performed on an independent replication cohort composed of 130 BD cases and 600 additional controls. The strongest association signals were observed in the HLA class I region, being HLA-B*51 the highest peak (overall P = 6.82E-32, OR = 3.82). A step-wise conditional logistic regression with classical alleles identified HLA-B*57 and HLA-A*03 as additional independent markers. The amino acid model that best explained the association, includes the position 97 of the HLA-B molecule and the position 66 of the HLA-A. Among the non-HLA loci, the most significant in the discovery analysis were: IL23R (rs10889664: P = 3.81E-12, OR = 2.00), the JRKL/CNTN5 region (rs2848479: P = 5.00E-08, OR = 1.68) and IL12A (rs1874886: P = 6.67E-08, OR = 1.72), which were confirmed in the validation phase (JRKL/CNTN5 rs2848479: P = 3.29E-10, OR = 1.66; IL12A rs1874886: P = 1.62E-08, OR = 1.61). Our results confirm HLA-B*51 as a primary-association marker in predisposition to BD and suggest additional independent signals within the class I region, specifically in the genes HLA-A and HLA-B. Regarding the non-HLA genes, in addition to IL-23R, previously reported in our population; IL12A, described in other populations, was found to be a BD susceptibility factor also in Spaniards; finally, a new associated locus was found in the JRKL/CNTN5 region.
metadata.dc.identifier.doi: 10.1371/journal.pone.0161305
Appears in Collections:Producción 2020

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