Lee Yun Jong, Kang Seong Wook, Song Ju Kyoung, Baek Han Joo, Choi Hyo Jin, Bae Young Deok, Ryu Hee Jung, Lee Eun Young, Lee Eun Bong, Song Yeong Wook
Department of Internal Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Hum Immunol. 2007 Sep;68(9):770-8. doi: 10.1016/j.humimm.2007.06.002. Epub 2007 Jul 17.
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.
干扰素调节因子-1（IRF-1）是一种转录因子，可调节I型和II型干扰素的功能，并在宿主保护中发挥作用。白塞病（BD）是一种特发性全身性血管炎，常伴有血栓形成特征，长期以来一直认为感染因子是其发病机制中的疾病触发因素。作者调查了105例BD患者（平均年龄41.7±标准误1.1岁，男性44例，女性61例）和105例年龄和性别匹配的健康对照者中IRF-1启动子-415 C/A、-410 A/G和-300 A/G以及3'非翻译区（UTR）A/G多态性的分布情况。对照组和BD组之间个体等位基因和基因型的频率没有差异。然而，BD患者中AGGG单倍型的频率显著更高（73.5%对60.2%，优势比[OR]=1.842，95%置信区间[95%CI]=1.219-2.783，p(c)=0.036），而CAAG单倍型的频率显著更低（2.2%对9.5%，OR=0.195，95%CI=0.068-0.559，p(c)=0.02）。此外,女性BD患者中AGGG单倍型的频率显著更高（80.3%对57.4%，OR=3.033，95%CI=1.716-5.360，p(c)=0.001），而CAAG单倍型的频率显著更低（0.8%对12.3%；OR=0.059，95%CI=0.010-0.357，p(c)=0.005）。通过亚组分析，CAAA单倍型在中度或重度BD患者中比轻度患者中更常见（25.4%对13.6%，OR=2.158，95%CI=1.046-4.440，Bonferroni校正前p=0.037）。当根据深静脉血栓形成（DVT）病史对BD患者进行亚分类时，发现CAAA单倍型显著增加了DVT的风险（42.1%对15.7%，OR=3.906，95%CI=1.836-8.324，p(c)=0.0015），而AGGG单倍型倾向于降低这种风险（57.9%对77.3%，OR=0.403，95%CI=0.195-0.834，p(c)=0.0685）。此外，经历过血栓形成事件的BD患者中CAAA单倍型的频率显著高于未经历过血栓形成事件的患者（40.5%对15.5%，OR=3.7147，95%CI=1.778-7.770，p(c)=0.0015）。这些结果表明，IRF-1是BD尤其是女性中的一个新的易感基因，此外，IRF-1多态性可能与BD患者的血栓形成有关。
