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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.

plos one

Genetic Analysis with the Immunochip Platform in Behçet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci