Multiple sclerosis and hepatitis C virus infection are associated with single nucleotide polymorphisms in interferon pathway genes
Multiple sclerosis and hepatitis C virus infection are associated with single nucleotide polymorphisms in interferon pathway genes
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DOI：
10.1089/jir.2007.0049
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发表时间：
2008-03-01
影响因子：
2.3
通讯作者：
Sacchetti, Lucia
中科院分区：
文献类型：
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作者：
Fortunato, Giuliana;Calcagno, Giuseppe;Sacchetti, Lucia
我们研究了干扰素（IFN）通路中的35个单核苷酸多态性（SNP），以确定它们对多发性硬化症（MS）和丙型肝炎病毒（HCV）感染的影响。共有182名多发性硬化症患者、103名慢性丙型肝炎患者和118名对照受试者参与了这项研究。在研究的35个SNP中，3个位于干扰素-α/β受体（IFNAR - 1），10个位于干扰素-α/β受体（IFNAR - 2），9个在Stat1，5个在Stat2，8个在干扰素调节因子 - 1（IRF - 1）。与对照组相比，Stat1基因多态性在多发性硬化症患者（rs#2066802比值比 = 7.46，95%置信区间 = 2.22 - 25.10；rs#1547550比值比 = 1.69，95%置信区间 = 1.01 - 2.81）和丙型肝炎患者（rs#2066802比值比 = 5.95，95%置信区间 = 1.55 - 22.81；rs#1547550比值比 = 2.30，95%置信区间 = 1.24 - 4.24）中明显更常见。此外，一个IRF - 1基因SNP与多发性硬化症相关（rs#2070721比值比 = 2.05，95%置信区间 = 1.03 - 4.09），四个IRF - 1基因SNP与丙型肝炎感染相关（rs#2070721比值比 = 2.59，95%置信区间 = 1.23 - 5.43；rs#2070723比值比 = 4.8，95%置信区间 = 1.26 - 18.20；rs#2070728比值比 = 9.81，95%置信区间 = 1.21 - 79.4；rs#2070729比值比 = 3.6，95%置信区间 = 1.23 - 10.48；rs#839比值比 = 4.67，95%置信区间 = 1.29 - 16.87）。单条染色体上的特征性核苷酸组合（单倍型）形成了包括SNP在内的模块结构，患者和对照组之间存在差异。使用排列检验来检测组间单倍型分布的差异，IRF - 1基因中的CCATTGA和CCGAA单倍型在多发性硬化症患者（p = 0.03）和丙型肝炎患者（p = 0.001）中比对照组更常见。总之，我们的数据表明，干扰素通路中IRF - 1和Stat1基因的遗传变异与多发性硬化症和丙型肝炎感染相关。
We have studied 35 single nucleotide polymorphisms (SNPs) in the interferon (IFN) pathway to determine their contribution to multiple sclerosis (MS) and hepatitis C virus (HCV) infection. A total of 182 patients with MS, 103 patients with chronic hepatitis C, and 118 control subjects were enrolled in the study. Of the 35 SNPs studied, 3 were in IFN-alpha/beta receptor (IFNAR-1), 10 in IFN-alpha/beta receptor (IFNAR-2), 9 in Stat1, 5 in Stat2, and 8 in IFN regulatory factor-1 (IRF-1). Compared to controls, Stat1 gene polymorphisms were significantly more frequent in MS patients (rs# 2066802 OR = 7.46, 95% CI = 2.22-25.10; rs# 1547550 OR = 1.69, 95% CI = 1.01-2.81) and in HCV patients (rs# 2066802 OR = 5.95, 95% CI = 1.55-22.81; rs# 1547550 OR = 2.30, 95% CI = 1.24-4.24). Also one IRF-1 gene SNP was associated with MS (rs# 2070721 OR = 2.05, 95% CI = 1.03-4.09), and four IRF-1 gene SNPs were associated with HCV infection (rs# 2070721 OR = 2.59, 95% CI = 1.23-5.43; rs# 2070723 OR = 4.8, 95% CI = 1.26-18.20; rs# 2070728 OR = 9.81, 95% CI = 1.21-79.4; rs# 2070729 OR = 3.6, 95% CI = 1.23-10.48; rs# 839 OR = 4.67, 95% CI = 1.29-16.87). Characteristic nucleotide combinations on single chromosomes (haplotype) generated block structures, including SNPs, that differed between patients and controls. Using a permutation test to detect differences in haplotype distribution between groups, the CCATTGA and the CCGAA haplotypes in the IRF-1 gene were more frequent in MS (p = 0.03) and in HCV patients (p = 0.001) than in controls. In conclusion, our data show that genetic variants in the IRF-1 and Stat1 genes of the IFN pathway are associated with MS and HCV infection.