HLA and non-HLA genes in Behçet's disease: a multicentric study in the Spanish population.

INTRODUCTION According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet's disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations. METHODS This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ(2) test. RESULTS In addition to HLA-B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be protective. Other HLA-A and B specificities were suggestive of association with the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58). Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs in IL10 were found to be significantly associated with susceptibility to BD in our population. CONCLUSION Different HLA specificities are associated with Behçet's disease in addition to B*51. Other non-HLA genes, such as IL23R and IL-10, play a role in the susceptibility to the disease.

Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't;

Fondo de Investigaciones Sanitarias (10/1701), Fondos FEDER, Plan Andaluz de Investigación (CTS-0197 and CTS-180), Red Enfermedades Inflamatorias y Reumáticas RD08/0075/0013 and Consejería de Salud de la Junta de Andalucía (PI0411/2010). LOF is the recipient of a fellowship (FI11/00547). The authors thank Asociación Andaluza de Enfermedades Autoinmunes (AADEA) and all patients and donors enrolled in the present study for their cooperation. Also, the authors thank the following public Spanish institutions for their participation in this study: Servicio Andaluz de Salud (Hospitales Torrecárdenas, Almería; Clínico San Cecilio, Granada; Carlos Haya, Málaga, and Virgen del Rocío and Valme, Sevilla), Servei Catalá de la Salut (Clinic and Vall d’Hebron hospitals, Barcelona), Servizo Galego de Saude (Complejo Hospitalario Universitario, A Coruña), Servicio Cántabro de Salud (Hospital Marqués de Valdecilla, Santander), Servicio Navarro de Salud (Hospital Virgen del Camino, Pamplona), Servicio Montes-Cano et al. Arthritis Research & Therapy 2013, 15:R145