HLA-DQA1等位基因多态性与慢性丙型肝炎的相关性  

Relationship between the polymorphism of HLA-DQA1 gene and chronic hepatitis C

作　　者：杨志明[1] 赵剑平[2] YANG Zhiming;ZHAO Jianping(Department of Clinical Laboratory,Handan Central Hospital,Handan 056000,China;Department of Ophthalmology,Handan Central Hospital)

机构地区：[1]邯郸市中心医院检验科,邯郸056000 [2]邯郸市中心医院眼科

出　　处：《山西医科大学学报》2019年第6期719-722,共4页Journal of Shanxi Medical University

基　　金：邯郸市科技计划项目(1323108129)

摘　　要：目的探讨人类白细胞抗原(HLA)-DQA1等位基因多态性与慢性丙型肝炎之间的相关性,并进一步明确HLA-DQA1与慢性丙型肝炎患者血清丙氨酸氨基转移酶(ALT)水平的关系以及与干扰素疗效的关系。方法采用序列特异性PCR(PCR-SSP)方法检测HLA-DQA1等位基因分型情况,比较171例慢性丙型肝炎患者(分为69例ALT正常组和102例ALT升高组)与162例健康对照组HLA-DQA1等位基因多态性差异。171例慢性丙型肝炎患者均采用聚乙二醇干扰素α-2a(PEGIFNα-2a)与利巴韦林(RBV)联合抗病毒治疗,治疗48周,随访6个月,以获得持续病毒学应答(SVR)为治疗有效,比较不同疗效组间HLA-DQA1等位基因频率分布。结果慢性丙型肝炎组HLA-DQA1*0103等位基因频率显著低于健康对照组(P<0.05),HLA-DQA1*0101/0102/0104/0201/0301/0302/0401/0501/0601等位基因在两组间比较差异无统计学意义(P>0.05);慢性丙型肝炎组患者中,ALT正常组HLA-DQA1*0501等位基因频率明显高于持续ALT升高组(P<0.05),HLA-DQA1*0101/0102/0103/0104/0201/0301/0302/0401/0601等位基因差异无统计学意义(P>0.05);慢性丙型肝炎组患者中,获得SVR患者HLA-DQA1*0601等位基因频率明显高于未获得SVR患者(P<0.05),HLA-DQA1*0101/0102/0103/0104/0201/0301/0302/0401/0501等位基因差异无统计学意义(P>0.05)。结论HLA-DQA1*0103可能是慢性丙型肝炎的拮抗基因;HLA-DQA1*0501可能会抑制ALT升高,从而减缓病程发展和进行性肝损伤;HLA-DQA1*0601等位基因可能不利于PEGIFNα-2a和RBV联合抗病毒治疗的应答。Objective To explore the relationship between HLA-DQA1 allele polymorphism and chronic hepatitis C,and to further clarify the relationship between HLA-DQA1 and serum alanine aminotransferase(ALT)level in patients with chronic hepatitis C and the efficacy of interferon.Methods The HLA-DQA1 allele genotyping was detected by PCR-SSP.The difference of HLA-DQA1 allele polymorphism between 171 patients with chronic hepatitis C(69 normal ALT patients and 102 elevated ALT patients)and 162 healthy controls was compared.Totally 171 patients with chronic hepatitis C were treated with PEG interferonα-2a(PEG IFNα-2a)combined with ribavirin(RBV)for 48 weeks and followed up for 6 months.With sustained virological response(SVR)as effective in treatment,the allele frequencies of HLA-DQA1 among different therapeutic groups were compared.Results The frequency of HLA-DQA1*0103 allele in chronic hepatitis C group was significantly lower than that in healthy control group(P<0.05),and there was no significant difference in other alleles between the two groups(P>0.05).In chronic hepatitis C patients,the frequency of HLA-DQA1*0501 allele in ALT normal group was significantly higher than that in persistent ALT elevation group(P<0.05),but there was no significant difference in other alleles between the two groups(P>0.05).In chronic hepatitis C patients,the frequency of HLA-DQA1*0601 allele in patients with SVR was significantly higher than that in patients without SVR(P<0.05),but there was no significant difference in other alleles(P>0.05).Conclusion HLA-DQA1*0103 may be an antagonistic gene of chronic hepatitis C.HLA-DQA1*0501 may inhibit the elevation of ALT,so as to slow down the course of disease development and progressive liver injury.HLA-DQA1*0601 allele may be detrimental to the response to combined antiviral therapy of PEG IFNα-2a and RBV.

关 键 词：HLA-DQA1 基因多态性 慢性丙型肝炎 ALT 干扰素 

分 类 号：R512.63[医药卫生—内科学]