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

Marco Antonio Montes-Cano1, Marta Conde-Jaldón1, José Raul García-Lozano1, Lourdes Ortiz-Fernández1, Norberto Ortego-Centeno2, María Jesús Castillo-Palma3, Gerard Espinosa4, Genaro Graña-Gil5, Miguel Angel González-Gay6, Ana Celia Barnosi-Marín7, Roser Solans8, Patricia Fanlo9, Teresa Camps10, Santos Castañeda11, Juan Sánchez-Bursón12, Antonio Núñez-Roldán1, Javier Martín13 and María Francisca González-Escribano1*

Author affiliations

1 Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain

2 Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada, Spain

3 Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain

4 Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain

5 Servicio de Reumatología, CHU A Coruña, Coruña, Spain

6 Servicio de Reumatología, Hospital Marques de Valdecilla, Santander, Spain

7 Servicio de Medicina Interna, Hospital Torrecárdenas, Almería, Spain

8 Servicio de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain

9 Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona, Spain

10 Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain

11 Servicio de Reumatología, Hospital de la Princesa, Madrid, Spain

12 Servicio de Reumatología, Hospital de Valme, Sevilla, Spain

13 IPB López Neyra, Granada, Spain

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Citation and License

Arthritis Research & Therapy 2013, 15:R145  doi:10.1186/ar4328

Published: 4 October 2013



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.


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 χ2 test.


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.


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.