Zavaglia C, Martinetti M, Silini E, Bottelli R, Daielli C, Asti M, Airoldi A, Salvaneschi L, Mondelli M U, Ideo G
Department of Internal Medicine and Center for Liver Diseases, Niguarda Hospital, Milan, Italy.
J Hepatol. 1998 Jan;28(1):1-7. doi: 10.1016/s0168-8278(98)80195-5.
BACKGROUND/AIMS: Recent studies have suggested that the course of chronic hepatitis C may be influenced by the immunogenetic background of the host. Specifically, HLA-DR11 (5) has been associated with less advanced hepatitis C virus (HCV)-related liver disease. The aim of the present study was to investigate whether HLA-DRB1*11 subtypes or HLA-DQA1 and DQB1 genes might be associated with protection from or susceptibility to chronic HCV infection, histological severity of HCV-induced liver disease and infecting HCV genotype.
Ninety-nine unrelated outpatients with histologically documented chronic hepatitis C were studied and their allele frequencies were compared with those of 179 ethnically matched controls and with those of 41 HCV RNA-positive patients with persistently normal aminotransferase levels (HCV carriers). HLA-DQ types and HLA-DRB1*11 subtypes were determined by polymerase chain reaction gene amplification with sequence specific primers.
None of 10 DQA1 or 12 DQB1 alleles was significantly associated with susceptibility to or protection from chronic HCV infection or with histological staging or with HCV genotype. However, analysis of DQA1-DQB1 combinations showed that DQA10201-DQB10201 combination was significantly more frequent in patients compared to controls, both in cis (26.3% vs 16.2%, p = 0.04, odds ratio = 1.8, 95% confidence interval, 0.96-3.5) and in trans (12.1% vs. 1.1%, p = 0.0001, OR = 12.2, 95% CI, 2.6-113.7). HCV carriers did not differ from controls or from patients in the frequency of DQA1-DQB1 combinations. The extended haplotype DRB11104, DQA10501, DQB1*0301 was seen significantly less frequently in patients than in controls (8% vs 22.3%, p = 0.0025, OR = 0.31, 95% CI, 0.12-0.7) or HCV-RNA carriers (8% vs 26.8%, p = 0.003, OR = 0.24, 95% CI, 0.08-0.73).
Immunogenetic factors may play a role in determining both protection from and susceptibility to chronic hepatitis C, the trans-dimer DQA10201-DQB10201 predisposing to and the DRB11104, DQA10501, DQB1*0301 haplotype protecting from chronic hepatitis C.
背景/目的：近期研究表明，慢性丙型肝炎的病程可能受宿主免疫遗传背景的影响。具体而言，HLA - DR11(5)与丙型肝炎病毒（HCV）相关肝病进展程度较低有关。本研究的目的是调查HLA - DRB1*11亚型或HLA - DQA1和DQB1基因是否与慢性HCV感染的易感性或抵抗力、HCV所致肝病的组织学严重程度以及感染的HCV基因型相关。
对99例经组织学证实的慢性丙型肝炎门诊患者进行研究，并将其等位基因频率与179例种族匹配的对照者以及41例丙氨酸转氨酶水平持续正常的HCV RNA阳性患者（HCV携带者）的等位基因频率进行比较。采用序列特异性引物的聚合酶链反应基因扩增法确定HLA - DQ类型和HLA - DRB1*11亚型。
10种DQA1等位基因或12种DQB1等位基因中，无一与慢性HCV感染的易感性或抵抗力、组织学分期或HCV基因型显著相关。然而，对DQA1 - DQB1组合的分析显示，DQA10201 - DQB10201组合在患者中的出现频率显著高于对照者，无论是顺式（26.3%对16.2%，p = 0.04，优势比 = 1.8，95%置信区间，0.96 - 3.5）还是反式（12.1%对1.1%，p = 0.0001，OR = 12.2，95% CI，2.6 - 113.7）。HCV携带者在DQA1 - DQB1组合频率上与对照者或患者无差异。扩展单倍型DRB11104、DQA10501、DQB1*0301在患者中的出现频率显著低于对照者（8%对22.3%，p = 0.0025，OR = 0.31，95% CI，0.12 - 0.7）或HCV - RNA携带者（8%对26.8%，p = 0.003，OR = 0.24，95% CI，0.08 - 0.73）。
免疫遗传因素可能在决定慢性丙型肝炎的抵抗力和易感性方面发挥作用，反式二聚体DQA10201 - DQB10201易导致慢性丙型肝炎，而单倍型DRB11104、DQA10501、DQB1*0301则对慢性丙型肝炎具有保护作用。
