人类白细胞抗原Ⅱ基因对乙型肝炎病毒易感性和干扰素抗病毒治疗的影响  

Influences of human leukocyte antigen class Ⅱ alleles on susceptibility to hepatitis B virus(HBV) infection and response to interferon treatment with HBV infection

作　　者：韩永年[1] 杨金龙[1] 郑水根[1] 汤群[1] 游龙英 张工梁[2] 杨影[2] 

机构地区：[1]海市第八人民医院传染病科肝病研究室,200233 [2]上海市血液中心输血研究所

出　　处：《上海医学》2004年第6期417-420,共4页Shanghai Medical Journal

基　　金：上海市科技发展基金资助项目 ( 0 14 1190 5 2 )

摘　　要：目的　探讨人类白细胞抗原 (HLA) DRB1和 DQB1等位基因多态性是对乙型肝炎病毒 (HBV)易感性及干扰素 (IFN)抗HBV治疗的影响。方法　应用聚合酶链反应 序列特异性引物 (PCR SSP)技术检测上海地区 6 9例慢性乙型肝炎 (CHB)患者的HLA DRB1和 DQB1等位基因以及 2 0 0名健康准骨髓捐献者的HLA DRB1等位基因。其中 32例接受α 1b干扰素治疗 2 4周。结果　CHB患者HLA DRB1 0 6和 DRB1 0 8等位基因的频度高于健康人 (2 .17%对 0 % ,RR =3.96 3,95 %CI :3.4 2 5～ 4 .5 85 ,P =0 .0 17;11.5 9%对 5 .5 0 % ,RR=2 .2 5 3,95 %CI:1.14 7～ 4 .4 2 8,P =0 .0 2 1) ;而DRB1 0 7等位基因的频度则低于健康人 (2 .90 %对 7.75 % ,RR=0 .35 5 ,95 %CI:0 .12 3～ 1.0 2 5 ,P =0 .0 4 7)。IFN治疗的患者中 ,10例应答者DRB1 14等位基因频度高于 2 2例非应答者 (2 0 .0 %对 2 .3% ,RR =10 .75 0 ,95 %CI :1.116～ 10 3.5 5 8,P =0 .0 30 ) ;而DQB1 0 7分布则相反(10 .0 %对 38.6 % ,RR =0 .176 ,95 %CI :0 .0 36～ 0 .85 6 ,P =0 .0 2 2 )。结论　HLA等位基因多态性可能与上海地区人群HBV的易感性和IFN抗HBV治疗有关。与其他HLA DRB1等位基因比较 ,HLA DRB1 0 6和 DRB1 0 8可能与HBV易感性有关 ,而HLA DRB1 0 7则相反 ,?Objective To appraise the influencesn of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles polymorphism on the genetic susceptibility to hepatitis B virus (HBV) infection and the response to interferon (IFN) therapy. Methods Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to determine HLA-DRB1 and -DQB1 genes in 68 patients with chronic hepatitis B and HLA-DRB1 in 200 healthy subjects ready to be bone marrow donor in Shanghai area. Among the patients with HBV infection, 32 were treated with IFN α-1b for 24 weeks.Results The frequencies of both HLA-DRB1*06 and -DRB1*08 alleles in 69 patients were higher than those in 200 healthy subjects (2.17% vs 0%, RR=3.963, 95%CI:3.425～4.585, P=0.017,and 11.59% vs 5.50%, RR= 2.253, 95%CI:1.147～4.428, P=0.021, respectively); whereas that of DRB1*07 allele was lower (2.90% vs 7.75%, RR=0.355,95%CI:0.123～1.025, P=0.047). The frequency of HLA-DRB1*14 allele was higher in 10 IFN responders than that in 22 non-responders(20.0% vs 2.3%, RR=10.750, 95%CI: 1.116～103.558, P=0.030), whereas that of DQB1*07 allele distribution was on the contrary(10.0% vs 38.6%, RR=0.176, 95%CI:0.036～0.856, P=0.022).Conclusions The polymorphism of HLA class Ⅱ may be associated with the susceptibility to HBV infection and the patient's response to IFN in Shanghai area. After comparing with other HLA-DRB1 alleles, HLA-DRB1*06 and DRB1*08 may be associated with chronicity of HBV infection. On the contrary HLA-DRB1*07 may provide protection against HBV infection, and HLA-DRB1*14 allele may be associated with a higher rate of response to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQB1*07 may be associated with low response rate to IFN.

关 键 词：人类白细胞抗原Ⅱ基因 乙型肝炎病毒易感性 干扰素 抗病毒治疗 乙型肝炎 

分 类 号：R512.62[医药卫生—内科学]