title: HLA and non-HLA genes in Behçet's disease: a multicentric study in the Spanish population.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Montes-Cano
authors.forename: Marta
authors.initials: M
authors.lastname: Conde-Jaldón
authors.forename: José Raul
authors.initials: JR
authors.lastname: García-Lozano
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ortiz-Fernández
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Castillo-Palma
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Genaro
authors.initials: G
authors.lastname: Graña-Gil
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Ana Celia
authors.initials: AC
authors.lastname: Barnosi-Marín
authors.forename: Roser
authors.initials: R
authors.lastname: Solans
authors.forename: Patricia
authors.initials: P
authors.lastname: Fanlo
authors.forename: Teresa
authors.initials: T
authors.lastname: Camps
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Juan
authors.initials: J
authors.lastname: Sánchez-Bursón
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldán
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: María Francisca
authors.initials: MF
authors.lastname: González-Escribano
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015797:HLA-B35 Antigen / Q000235:genetics; D059949:HLA-B51 Antigen / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D012307:Risk Factors; D013030:Spain
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; D059949:HLA-B51 Antigen; C103707:HLA-B57 antigen; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D016753:Interleukin-10