Ortiz-Fernández, LourdesCarmona, Francisco-DavidMontes-Cano, Marco-AntonioGarcía-Lozano, José-RaúlConde-Jaldón, MartaOrtego-Centeno, NorbertoCastillo, María JesúsEspinosa, GerardGraña-Gil, GenaroSánchez-Bursón, JuanJuliá, María RosaSolans, RoserBlanco, RicardoBarnosi-Marín, Ana-CeliaGómez de la Torre, RicardoFanlo, PatriciaRodríguez-Carballeira, MónicaRodríguez-Rodríguez, LuisCamps, TeresaCastañeda, SantosAlegre-Sancho, Juan-JoseMartín, JavierGonzález-Escribano, María Francisca2016-10-142016-10-142016-08-22Ortiz-Fernández L, Carmona FD, Montes-Cano MA, García-Lozano JR, Conde-Jaldón M, Ortego-Centeno N, et al. Genetic Analysis with the Immunochip Platform in Behçet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci. PLoS ONE. 2016; 11(8):e0161305http://hdl.handle.net/10668/2469Journal Article;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.enAlelosAminoácidosSíndrome de BehçetGenes clase I del complejo de histocompatibilidad (MHC)GenotipoAntígenos HLA-BModelos logísticosEspañaMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino AcidsMedical Subject Headings::Diseases::Stomatognathic Diseases::Mouth Diseases::Behcet SyndromeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Major Histocompatibility Complex::Genes, MHC Class IMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-B AntigensMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic ModelsMedical Subject Headings::Geographicals::Geographic Locations::Europe::Spainresearch article27548383open access10.1371/journal.pone.01613051932-6203PMC4993481