MHC class II genes influence the susceptibility to chronic active hepatitis C

MHC class II genes influence the susceptibility to chronic active hepatitis C
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DOI:
10.1016/s0168-8278(97)80169-9
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发表时间:
1997-08-01
影响因子:
25.7
通讯作者:
Rittner, C
Rittner, C
中科院分区:
医学1区
文献类型:
--
作者:
Hohler, T;Gerken, G;Rittner, C

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背景/目的:超过70%的丙型肝炎病毒感染者发生慢性丙型肝炎,病毒因素影响病程,但宿主因素的重要性知之甚少。方法:分析两组慢性丙型肝炎病毒感染者和对照组主要组织相容性复合体(MHC)I类和IT类抗原的频率。采用标准的微量淋巴细胞毒试验进行MHC-I类分型。结果:75例慢性丙型肝炎患者中有26例(34.7%)存在DRB1*0301基因,而在10 1例正常对照中有12例(11.9%),其相对危险度为3.9%(P<0.0 1)。该等位基因的纯合子似乎提供了更强的风险,相反,DRB1*1301在3名持续感染的受试者中被检测到(4.0%),而在21名对照受试者中被检测到(20.8%)(相对风险0.2p&lt;0.008)。该等位基因与DQA1*0103连锁,10例患者(13.3%)与34例对照组(33.7%)有关联(相对危险度为0.31p&lt;0.003)。DRB1*1301和DQA1*0103的存在提供了更强的保护作用(相对风险为0.08;p&lt;0.005)。结论:MHCⅡ类等位基因DRB1*0301易进展为慢性活动性丙型肝炎,而Ⅱ类等位基因DRB1*1301和DQA1*0103对慢性活动性感染有保护作用。
Background/Aims: Chronic hepatitis C develops in more than 70% of hepatitis C virus infected subjects, Viral factors influence the disease course, but little is known about the importance of host factors.Methods: Frequencies of major histocompatibility complex (MHC) class I and class IT antigens were analyzed in two groups of patients with chronic hepatitis C virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotyping was done by PCR based typing methods.Results: DRB1*0301 was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%) and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p < 0.001). Homozygosity for this allele appeared to confer a stronger risk, In contrast, DRB1*1301 was detected in three subjects with persistent infection (4.0%) compared to 21 control subjects (20.8%) (relative risk 0.2; p < 0.008). This allele was linked with DQA1*0103, which was found in 10 patients (13.3%) compared to 34 control subjects (33.7%) (relative risk 0.31; p < 0.003). An even stronger protective effect was provided by the presence of DRB1*1301 and DQA1*0103 (relative risk 0.08; p < 0.005). These findings were confirmed in a second group of chronic hepatitis C virus infected patients.Conclusions: The MHC class II allele DRB1*0301 appears to predispose to progression to chronic active hepatitis C, whereas the class II. alleles DRB1*1301 and DQA1*0103 appear to provide protection against chronic active infection,vith hepatitis C virus.