title: Associations between interferon regulatory factor-1 polymorphisms and Behçet's disease.
abstract: Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates the functions of type I and II interferons and plays a role in host protection. Behçet's disease (BD) is an idiopathic systemic vasculitis that is often complicated with thrombotic features, and infectious agents have long been postulated to be a disease-triggering factor in its pathogenesis. The authors investigated the distributions of IRF-1 promoter -415 C/A, -410 A/G, and -300 A/G, and 3'-untranslated region (UTR) A/G polymorphisms in 105 BD patients (mean age 41.7 +/- SEM 1.1 years, 44 male and 61 female) and in 105 gender- and age-matched healthy controls. The frequencies of individual alleles and genotypes were not different between the control and BD groups. However, the frequency of AGGG haplotype was significantly higher (73.5% vs 60.2%, odds ratio [OR] = 1.842, 95% confidence interval [95% CI] = 1.219-2.783, p(c) = 0.036) and that of the CAAG haplotype was significantly lower (2.2% vs 9.5%, OR = 0.195, 95% CI = 0.068-0.559, p(c) = 0.02) in BD patients than in healthy controls. In addition, the frequency of the AGGG haplotype was significantly higher (80.3% vs 57.4%, OR = 3.033, 95% CI = 1.716-5.360, p(c) = 0.001) and that of the CAAG haplotype was significantly lower (0.8% vs 12.3%; OR = 0.059, 95% CI = 0.010-0.357, p(c) = 0.005) in female BD patients than female controls. By subgroup analyses, the CAAA haplotype tended to be more common in BD patients with moderate or severe disease than in those with mild disease (25.4% vs 13.6%, OR = 2.158, 95% CI = 1.046-4.440, p = 0.037 before Bonferroni correction). When BD patients were subclassified by a history of deep vein thrombosis (DVT), the CAAA haplotype was found to be significantly increased the risk of DVT (42.1% vs 15.7%, OR = 3.906, 95% CI = 1.836-8.324, p(c) = 0.0015) and the AGGG haplotype tended to reduce this risk (57.9% vs 77.3%, OR = 0.403, 95% CI = 0.195-0.834, p(c) = 0.0685). Furthermore, the frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event than in those that had not (40.5% vs 15.5%, OR = 3.7147, 95% CI = 1.778-7.770, p(c) = 0.0015). These results suggest that IRF-1 is a novel susceptibility gene in BD, especially in women, and furthermore, that IRF-1 polymorphisms may be related to thrombosis in BD patients.
authors.affiliation: Department of Internal Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yun Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Ju Kyoung
authors.initials: JK
authors.lastname: Song
authors.forename: Han Joo
authors.initials: HJ
authors.lastname: Baek
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Young Deok
authors.initials: YD
authors.lastname: Bae
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Ryu
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000235:genetics
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1