HLA-DPA1/B1基因多态性与丙型肝炎病毒易感性和感染转归的关联研究  

Association of HLA-DPA1/B1 gene polymorphisms with the susceptibility and outcomes of hepatitis C virus infection

作　　者：裴家平 季晓伟[1] 蒋龙凤[2] 邓小昭[1,3] 徐孝东[1] 肖雯[4] 丁伟良[5] 张锦海[3] 王长军[3] 朱丹燕[1] 李丙军[3] 

机构地区：[1]南京医科大学基础医学院生物化学与分子生物学系,江苏南京210029 [2]南京医科大学第一附属医院感染病科,江苏南京210029 [3]南京军区疾病预防控制中心疾病预防控制所,江苏南京210002 [4]中国药科大学生命科学与技术学院微生物与生化药学系,江苏南京210009 [5]宜兴市人民医院检验科,江苏宜兴214200

出　　处：《中华疾病控制杂志》2016年第2期112-115,120,共5页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81172724;30972628);"十二五"国家科技重大专项(2011ZX10004-902);江苏省自然科学基金(BK2010112;BK2011840);中国肝炎基金会天晴肝病研究基金(CFHPC20132071)

摘　　要：目的探讨江苏地区有偿献血高危人群白细胞抗原(human leukocyte antigen,HLA)-DP A1/B1基因多态性与丙型肝炎病毒(hepatitis C virus,HCV)感染转归的关联性。方法采用病例-对照(慢性丙型肝炎患者258人,自限清除者170人,健康对照者320人)研究,通过聚合酶链反应序列为基础的基因分型(polymerase chain reaction-sequence based genotyping,PCR-SBT)技术对3组人群HLA-DPA1/B1等位基因进行分析,并比较各等位基因频率。结果 HCV感染组的HLA-DPA1*0103与HLA-DPB1*0201等位基因频率高于健康对照组(40.7%vs32.2%,P=0.003)(22.0%vs 12.5%,P<0.001)。HCV持续感染组的HLA-DPA1*0201与HLA-DPB1*1401等位基因频率低于自限清除组(7.9%vs 13.8%,P=0.018)(0.0%vs 2.1%,P=0.015)。HLA-DPA1/B1单倍型分析发现,HCV感染组的DPB1*0501-DPA1*0103和DPB1*0201-DPA1*0103单倍型频率高于健康对照组(P<0.001)。而HCV感染组单倍型DPB1*0202-DPA1*0202的频率低于健康对照组(P<0.001)。HCV持续感染组的单倍型DPB1*0202-DPA1*0202的基因频率高于HCV自限清除组(P=0.004)。HCV持续感染组DPB1*0402-DPA1*0103单倍型频率又低于HCV自限清除组(P=0.008)。结论在江苏地区有偿献血高危人群中,HCV感染转归与HLA-DPA1/B1基因多态性之间存在一定关联性。Objective To explore the relationships between human leukocyte antigen（ HLA）-DP A1 /B1 gene polymorphisms with the susceptibility and the outcomes of hepatitis C virus（ HCV） infection among high-risk population in Jiangsu province. Methods HLA-DPA1 / B1 gene alleles were detected in 748 subjects including 170 spontaneous clearance of HCV infection,258 persistent HCV infections and 320 healthy controls by PCR-SBT,and the HLA alleles frequencies were compared between groups. Results The frequencies of HLA-DPA1＊ 0103 and HLA-DPB1＊ 0201 alleles were higher in HCV infection group than those in healthy control（ 40. 7% vs 32. 2%,P = 0. 003）（ 22. 0% vs 12. 5%,P〈 0. 001）. The frequencies of HLA-DPA1 ＊ 0201 and HLA-DPB1 ＊ 1401 alleles were lower in persistent HCV infection group than those in spontaneous clearance HCV infection group（ 7. 9% vs 13. 8%,P = 0. 018）（ 0. 0% vs 2. 1%,P =0. 015）. However,the data analyses showed that the frequencies of haplotype DPB1 ＊ 0501-DPA1 ＊ 0103 and DPB1 ＊0201-DPA1＊ 0103 were higher in HCV infection group than those in healthy control（ P 〈0. 001）,but the frequencies of haplotype DPB1＊ 0202-DPA1＊ 0202 were lower than those in healthy control（ P 〈0. 001）. Furthermore,the frequencies of haplotype DPB1＊ 0202-DPA1＊ 0202 were higher in persistent HCV infection group than those in spontaneous clearance HCV infection（ P = 0. 004）,while the frequencies of haplotype DPB1＊ 0402-DPA1＊ 0103 were lower in persistent HCV infection group than those in spontaneous clearance HCV infection（ P = 0. 008）. Conclusions HLA-DPA1 / B1 alleles might be associated with the susceptibility and the outcomes of HCV infection among population at high risk in Jiangsu Province.

关 键 词：肝炎病毒属 HLA抗原 基因频率 

分 类 号：R373.21[医药卫生—病原生物学] R512.63[医药卫生—基础医学]