Genetic Analysis with the Immunochip Platform in Behçet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci
Ortiz-Fernández, Lourdes (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Carmona, F. David (Instituto de Parasitología y Biomedicina "López-Neyra")
Montes-Cano, Marco-Antonio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
García-Lozano, José-Raúl (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Conde-Jaldón, Marta (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Ortego-Centeno, Norberto (Hospital Universitario San Cecilio (Granada))
Castillo, María Jesús (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Espinosa, Gerard (Hospital Universitari Clínic)
Graña, Jenaro (Complejo Hospitalario Universitario de A Coruña)
Sánchez-Bursón, Juan (Hospital Universitario Virgen de Valme (Sevilla, Andalusia))
Juliá, María Rosa (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Solans, Roser (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Blanco, Ricardo (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Barnosi-Marín, Ana-Celia (Complejo Hospitalario Torrecárdenas (Almeria))
Gómez de la Torre, Ricardo (Hospital Universitario Central de Asturias)
Fanlo, Patricia (Hospital Virgen del Camino (Pamplona))
Rodríguez-Carballeira, Mónica (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Rodriguez-Rodriguez, Luis (Hospital Clínico San Carlos (Madrid))
Camps i Miró, Teresa (Hospital Regional Universitario de Málaga)
Castañeda, Santos (Instituto de Investigación Hospital Universitario de la Princesa)
Alegre-Sancho, Juan José (Hospital Universitari Doctor Peset (València))
Martín, Javier (Instituto de Parasitología y Biomedicina "López-Neyra")
González-Escribano, María Francisca (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Universitat Autònoma de Barcelona

Data:	2016
Resum:	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.
Ajuts:	Instituto de Salud Carlos III 13/01118 Instituto de Salud Carlos III FI11/00547 Instituto de Salud Carlos III RD12/0009/0013
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 11 (august 2016) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0161305
PMID: 27548383

17 p, 1.6 MB

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