Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease
Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease
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DOI：
10.1002/hep.510290445
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发表时间：
1999-04-01
期刊：
影响因子：
13.5
通讯作者：
Silini, EM
中科院分区：
文献类型：
--
作者：
Asti, M;Martinetti, M;Silini, EM
丙型肝炎的结果可能与病毒因素和宿主的免疫反应有关。我们在三组受试者中将肝病的严重程度与人类白细胞抗原（HLA）基因（C4 A，C4 B，TNFA，TNFB，DRB 1，DRB 3，DRB 4，DRB 5，DQA 1，DQB 1，TAP 1和TAP 2）相关联：99例慢性肝炎患者，41例无症状携带者和179例未感染对照。3 - 4级肝炎患者的等位基因TNFB*1、DRB 1 *1104和DRB 3 *03频率较低，具有保护作用，而等位基因DRB 1 *1001频率较高，与疾病严重程度相关，HLA-DRB*11亚型的分布差异显著：DRB 1 *1104在携带者中最常见，而DRB 1 *1101在患者中更常见。TAP 1C，2A单倍型在患者中的代表性也低于对照组。最后，在DQB 1基因座携带者患者中观察到杂合子受试者减少。对应分析和多元Logistic回归的多变量分析表明，年龄，性别和丙型肝炎病毒（HCV）的类型是最强的危险因素，然而，一些免疫遗传学变量（TNFB*1，DRB 1 *1101，和DRB 3 *03）显示了独立的贡献，特别是在比较极端的疾病表现的患者。不同HLA亚区中不同基因的参与表明，抗HCV反应是由复杂的基因相互作用而不是由单个等位基因调节的。
Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a protective role, and high frequency of allele DRB1*1001, which was associated with disease severity HLA-DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1101, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti-HCV responses are modulated by a complex gene interplay rather than by single alleles.