Document Detail


Association study of IL10 and IL23R-IL12RB2 in Iranian Behçet's disease patients.
MedLine Citation:
PMID:  22378604     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Independent replication of genome-wide association studies (GWAS) findings remains the gold standard for results validation. Our aim was to test the association of the interleukin 10 (IL10) gene and the interleukin 23 receptor (IL23R) - interleukin 12 receptor beta 2 (IL12RB2) locus previously identified as Behçet's disease (BD) risk factors in two GWAS (1,2). METHODS: Six haplotype tagging single nucleotide polymorphisms (SNPs) in IL10 and fortytwo in IL23R-IL12RB2 were genotyped in 973 BD patients and 637 controls. Population stratification was assessed using a panel of 86 ancestry informative markers. RESULTS: Subtle evidence of population stratification was found in our dataset. In IL10, rs1518111 was nominally associated with BD before and after adjusting for population stratification (p(unadj) =2.53E-02, OR(T) [95% CI]=1.20[1.02-1.40]; p(adj) =1.43E-02), and rs1554286 demonstrated a trend for association (p(unadj) =6.14E-02; padj=3.21E-02). Six SNPs in IL23R-IL12RB2 were associated with BD after Bonferroni's correction, the most significant of which were rs17375018 (p(unadj) =1.93E-06, OR(G) [95% CI]=1.51[1.27-1.78]), rs7517847 (p(unadj) =1.23E-06, OR(T) [95% CI]=1.48[1.26-1.74]), and rs924080 (p=1.78E-05, OR(T) [95% CI]=1.29[1.20-1.39]). rs7530511, rs6693831, and rs1495965 were also significantly associated in all tests performed. Meta-analyses with data from previous reports strengthen the role of rs1518111, rs17375018, rs7517847, and rs924080 in BD risk, but no epistatic interactions were detected between IL10 and IL23R-IL12RB2. Imputation analysis highlighted the importance of IL23R regulatory regions in BD susceptibility. CONCLUSIONS: Our study independently confirmed, extended and refined the association between BD, IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in BD as they may have novel therapeutic implications (e.g. immunosuppressive therapy targeted at IL23-p19).
Authors:
Joana M Xavier; Farhad Shahram; Fereydoun Davatchi; Alexandra Rosa; Jorge Crespo; Bahar Sadeghi Abdollahi; Abdolhadi Nadji; Gorete Jesus; Filipe Barcelos; José Vaz Patto; Niloofar Mojarad Shafiee; Fahmida Ghaderibarim; Sofia A Oliveira
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-29
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-3-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Affiliation:
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
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