2026-08-29T14:05:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/252132024-10-23T09:08:08Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Ortiz-Fernández, Lourdes
author
Carmona, Francisco-David
author
Montes-Cano, Marco-Antonio
author
García-Lozano, José-Raúl
author
Conde-Jaldón, Marta
author
Ortego-Centeno, Norberto
author
Castillo, María Jesús
author
Espinosa, Gerard
author
Graña-Gil, Genaro
author
Sánchez-Bursón, Juan
author
Juliá, María Rosa
author
Solans, Roser
author
Blanco, Ricardo
author
Barnosi-Marín, Ana-Celia
author
Gómez de la Torre, Ricardo
author
Fanlo, Patricia
author
Rodríguez-Carballeira, Mónica
author
Rodríguez-Rodríguez, Luis
author
Camps, Teresa
author
Castañeda, Santos
author
Alegre-Sancho, Juan-Jose
author
Martín, Javier
author
González-Escribano, María Francisca
2024-10-23T09:08:08Z
2024-10-23T09:08:08Z
2016-08-22
10.1371/journal.pone.0161305
1932-6203
PloS one
http://hdl.handle.net/10668/2469
27548383
https://hdl.handle.net/20.500.12105/25213
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.
eng
Genetic Analysis with the Immunochip Platform in Behcet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci
research article