title: Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.
abstract: OBJECTIVE
  Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor β2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS.
  
  
  METHODS
  Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers.
  
  
  RESULTS
  Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD.
  
  
  CONCLUSIONS
  These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19).
authors.affiliation: Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Xavier
authors.forename: Farhad
authors.initials: F
authors.lastname: Shahram
authors.forename: Fereydoun
authors.initials: F
authors.lastname: Davatchi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rosa
authors.forename: Jorge
authors.initials: J
authors.lastname: Crespo
authors.forename: Bahar Sadeghi
authors.initials: BS
authors.lastname: Abdollahi
authors.forename: Abdolhadi
authors.initials: A
authors.lastname: Nadji
authors.forename: Gorete
authors.initials: G
authors.lastname: Jesus
authors.forename: Filipe
authors.initials: F
authors.lastname: Barcelos
authors.forename: José Vaz
authors.initials: JV
authors.lastname: Patto
authors.forename: Niloofar Mojarad
authors.initials: NM
authors.lastname: Shafiee
authors.forename: Fahmida
authors.initials: F
authors.lastname: Ghaderibarim
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D000483:Alleles; D001528:Behcet Syndrome / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C508439:IL12RB2 protein, human; C515500:IL23R protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10