血HLA-A、-B、-C、-DRB1、-DQB1 等位基因多态性与肝细胞癌发生关联研究*

doi:10.3969/j.issn.1672-5069.2018.06.028

实用肝脏病杂志 ›› 2018, Vol. 21 ›› Issue (6): 940-946.doi: 10.3969/j.issn.1672-5069.2018.06.028

血HLA-A、-B、-C、-DRB1、-DQB1 等位基因多态性与肝细胞癌发生关联研究^*

欧阳石, 陈小平, 程涛, 钟宋, 刘崇文, 肖露露, 陈阳述

510700 广州市广州医科大学附属第五医院感染科（欧阳石）; 广州市解放军第458医院全军肝病中心（欧阳石,陈小平,程涛,钟宋,刘崇文,陈阳述）; 南方医科大学南方医院（肖露露）

收稿日期:2017-09-14 出版日期:2018-11-10 发布日期:2018-12-25
通讯作者: 陈阳述 E-mail：cys@vip.163.com
作者简介:欧阳石,副主任医师。主要从事病毒性肝炎及终末期肝病诊治研究。E-mail：ouyangshi2005@163.com;共同陈小平,主任医师。主要从事原发性肝癌的外科治疗及肝移植研究。E-mail：chenxp1967@sina.com
基金资助:
*广州市科学研究专项基金资助项目（编号：2014J4100034）; 广东省自然科学基金资助项目（编号：2015A030313684）; 广东省科技计划项目（编号：2014A020212451)

Correlation of HLA-A,-B,-C,-DRB1,-DQB1 alleles to hepatocellular carcinoma development in patients with hepatitis B viral infection

Ouyang Shi, Chen Xiaoping, Cheng Tao, et al.

Department of Infectious Disease,Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510700,Guangdong Province; The Department of Liver Disease,458TH Hospital,Guangzhou 510602,Guangdong Province

Received:2017-09-14 Online:2018-11-10 Published:2018-12-25

摘要/Abstract

摘要： 目的探讨中国广东汉族人血HLA-A、-B、-C、-DRB1、-DQB1等位基因与HBV感染罹患肝细胞癌（HCC）的关联性。方法采用聚合酶链反应-直接测序分型法检测广东地区56例HCC患者和97例健康志愿者血HLA-A、-B、-C、-DRB1、-DQB1基因型。结果 HCC患者血HLA- A*02:03和A*02:07等位基因频率明显高于健康人（0.116071对0.046392和0.178571对0.061856,x²=5.167、x²=10.33,P=0.023、P=0.001）;HCC患者血HLA-B*46:01等位基因频率为0.205357,明显高于健康人的0.108247（x²=5.439,P=0.02）;HCC患者血HLA- DRB1*14:54 和 DRB1*12:02等位基因频率明显高于健康人（0.089286对0和0.142857对0.06701,x²=14.502、x²=4.761,P=0.000、P=0.026）;HCC患者血HLA-DQB1*05:03等位基因频率为0.098214,明显高于健康人的0.036082（x²=4.951,P=0.026）;HCC患者血HLA-A*30:01等位基因频率为0.017857,明显低于健康人的0.082474（x²=5.355,P=0.021）;HCC患者血HLA-B*13:02等位基因频率为0.008929,明显低于健康人的0.07732（x²=6.702,P=0.01）。结论在中国广东地区人群中,HLA-A*02:03、A*02:07、HLA-B*46:01、HLA-DRB1*14:54、DRB1*12:02、HLA-DQB1*05:03与感染HBV的HCC发病有关,而与HLA-A*30:01和HLA-B*13:02可能无关。

关键词: 肝细胞癌, 人类白细胞抗原, 基因频率, 基因多态性

Abstract: Objective To analyze the correlation of HLA-A,-B,-C,-DRB1,-DQB1 allele polymorphisms to the development of hepatocellular carcinoma （HCC） in patients with hepatitis B. Methods 56 patients with HCC and underlying hepatitis B viral infection and 97 healthy persons were recruited in this study. Blood HLA-A,-B,-C,-DRB1,-DQB1 genes were detected by polymerase chain reaction sequence-based typing. Results The frequencies of HLA-A*02:03,A*02:07,HLA-B*46:01,HLA-DRB1*14:54,DRB1*12:02,HLA-DQB1*05:03 were significantly higher in patients with HCC than in the control,and they might be the risk factors for chronic hepatitis B patients developing HCC. While the frequencies of HLA-A*30:01 and HLA-B*13:02 were significantly lower in HCC group than in the control group. Conclusion In GuangDong province population,blood HLA-A*02:03,A*02:07,HLA-B*46:01,HL-DRB1*14:54,DRB1*12:02,HLA-DQB1*05:03 are positively correlated with the development of HCC.

Key words: Hepatocellular carcinoma, HLA, Alleles, Polymorphisms

欧阳石, 陈小平, 程涛, 钟宋, 刘崇文, 肖露露, 陈阳述. 血HLA-A、-B、-C、-DRB1、-DQB1 等位基因多态性与肝细胞癌发生关联研究^*[J]. 实用肝脏病杂志, 2018, 21(6): 940-946.

Ouyang Shi, Chen Xiaoping, Cheng Tao, et al.. Correlation of HLA-A,-B,-C,-DRB1,-DQB1 alleles to hepatocellular carcinoma development in patients with hepatitis B viral infection[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(6): 940-946.

参考文献

[1] Maynard J E. Hepatitis B:global importance and need for control. Vaccine,1990,8 (Suppl 1):S18-S20,S21-S23.
[2] El-Chennawi FA,Auf FA,Metwally SS,et al.HLA-class II alleles in Egyptian patients with hepatocellular carcinoma. Immunol Invest,2008,37(7):661-674.
[3] Lavanchy D.Hepatitis B virus epidemiology,disease burden,treatment,and current and emerging prevention and control measures. J Viral Hepat,2004,11(2):97-107.
[4] Dragani TA.Risk of HCC:genetic heterogeneity and complex genetics. J Hepatol,2010,52(2):252-257.
[5] Baglioni S,Genuardi M.Simple and complex genetics of colorectal cancer susceptibility. Am J Med Genet C Semin Med Genet,2004,129C(1):35-43.
[6] Dibbens LM,Heron SE,Mulley JC.A polygenic heterogeneity model for common epilepsies with complex genetics. Genes Brain Behav,2007,6(7):593-597.
[7] Fukusato T,Gerber MA,Thung SN,et al.Expression of HLA class I antigens on hepatocytes in liver disease. Am J Pathol,1986,123(2):264-270.
[8] Moroso V,van Cranenbroek B,Mancham S,et al. Prominent HLA-G expression in iver disease but not after liver transplantation. Transplantation,2015,99(12):2514-2522.
[9] Strom SC,Gramignoli R.Human amnion epithelial cells expressing HLA-G as novel cell-based treatment for liver disease. Hum Immunol,2016,77(9):734-739.
[10] Singh R,Kaul R,Kaul A,et al.A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J Gastroenterol,2007,13(12):1770-1787.
[11] Aptsiauri N,Cabrera T,Mendez R,et al.Role of altered expression of HLA class I molecules in cancer progression. Adv Exp Med Biol,2007,601:123-131.
[12] 中国抗癌协会肝癌专业委员会,中华医学会肝病学分会肝癌学组,中国抗癌协会病理专业委员会. 原发性肝癌规范化诊断指南. 中华肝胆外科杂志,2015,21:145-151.
[13] Hacibektasoglu A,Barut A,Inal A.Relationship of histocompatibility groups to chronic HBV infections. Mikrobiyol Bul,1993,27(3):241-248.
[14] Maynard JE. Hepatitis B:global importance and need for control. Vaccine,1990,(Suppl8):S18-20,discussion S21-23.
[15] Mothe B,Llano A,Ibarrondo J,et al.Definition of the viral targets of protective HIV-1-specific T cell responses. J Transl Med,2011,9:208.
[16] Begovich AB,Mcclure GR,Suraj VC,et al.Polymorphism,recombination,and linkage disequilibrium within the HLA class II region. J Immunol,1992,148(1):249-258.
[17] De Re V,Caggiari L,Simula M P,et al.Role of the HLA class II:HCV-related disorders. Ann N Y Acad Sci,2007,1107:308-318.
[18] Fallahi P,Ferri C,Ferrari S M,et al.Cytokines and HCV-related disorders. Clin Dev Immunol,2012,2012:468107.
[19] Longombardo G,Ferri C,Marchi S,et al.Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders. Clin Immunol Immunopathol,1998,87(2):124-129.
[20] Liu C,Cheng B.Association of polymorphisms of human leucocyte antigen-DQA1 and DQB1 alleles with chronic hepatitis B virus infection,liver cirrhosis and hepatocellular carcinoma in Chinese. Int J Immunogenet,2007,34(5):373-378.
[21] Donaldson PT,Ho S,Williams R,et al.HLA class II alleles in Chinese patients with hepatocellular carcinoma. Liver,2001,21(2):143-148.
[22] Xin YN,Lin ZH,Jiang XJ,et al.Specific HLA-DQB1 alleles associated with risk for development of hepatocellular carcinoma:a meta-analysis. World J Gastroenterol,2011,17(17):2248-2254.

血HLA-A、-B、-C、-DRB1、-DQB1 等位基因多态性与肝细胞癌发生关联研究^*

Correlation of HLA-A,-B,-C,-DRB1,-DQB1 alleles to hepatocellular carcinoma development in patients with hepatitis B viral infection

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	曹策, 郁义星, 王贝贝, 赵卫峰. 增强磁共振成像联合血清甲胎蛋白和脱-γ-羧基凝血酶原诊断肝细胞癌临床价值探讨[J]. 实用肝脏病杂志, 2019, 22(6): 896-899.
[2]	朱俊, 丁莹, 王世清, 张野, 刘野, 刘泽刚. 围手术期应用乌司他丁治疗对肝细胞癌患者肝切除术后外周血Th22细胞百分比和血浆白细胞介素-22的影响*[J]. 实用肝脏病杂志, 2019, 22(5): 720-723.
[3]	王刚, 赵洪波, 朱亚玲, 蒋保三, 张越美, 刁勇. 基于数据库分析肝细胞癌细胞XPO5基因水平变化及其临床意义*[J]. 实用肝脏病杂志, 2019, 22(5): 724-727.
[4]	戴青云, 王润东, 荚卫东. 术前预后营养指数评估肝细胞癌患者肝切除术后早期肿瘤复发价值探讨^*[J]. 实用肝脏病杂志, 2019, 22(4): 561-564.
[5]	杨富存, 尚怀学, 盖永浩. 钆塞酸二钠增强磁共振扫描诊断肝脏局灶性病变研究^*[J]. 实用肝脏病杂志, 2019, 22(4): 577-580.
[6]	彭新健, 肖玉辉, 许斯鼎, 石荣跃, 王耀政, 王瑜琳. 放射性肝损伤患者肝脏磁共振扩散加权成像表现特征分析[J]. 实用肝脏病杂志, 2019, 22(3): 373-376.
[7]	乔志忠. 超声造影定量分析鉴别肝脏局灶性结节性增生与原发性肝癌初步探讨[J]. 实用肝脏病杂志, 2019, 22(3): 421-424.
[8]	朱光曦（综述）, 文良志, 陈东风（审校）. 非酒精性脂肪性肝病相关肝细胞癌发病机制研究进展[J]. 实用肝脏病杂志, 2019, 22(3): 453-456.
[9]	袁春晖,李春雨,李红丽,赵红娜,王文红,孟庆旭,张中学. IL28B基因多态性对聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎患者疗效的影响[J]. 实用肝脏病杂志, 2019, 22(2): 184-187.
[10]	王虎明,樊东升,徐杰,刘险峰,周宁,丽敏,包娜娜. 肝细胞癌患者癌组织miRNA-30c水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2019, 22(2): 248-251.
[11]	幸奠奎,程婧. ¹⁸F-FDG PET/CT检查指标预测肝细胞癌微血管侵犯临床价值研究^*[J]. 实用肝脏病杂志, 2019, 22(2): 252-254.
[12]	王秀清,马艳君,詹晋莉. 肝动脉化疗栓塞术联合超声引导下微波消融术治疗特殊部位原发性肝癌患者疗效及安全性分析 ^*[J]. 实用肝脏病杂志, 2019, 22(2): 260-263.
[13]	张小舟,帅领,王庆大,杨楠. 接受TACE治疗的肝细胞癌患者血清miR-335水平变化及其对预后判断的价值分析^*[J]. 实用肝脏病杂志, 2019, 22(2): 268-271.
[14]	王朝霞,关珂,付三仙,王慧杰. 肠内肠外联合营养支持治疗肝细胞癌患者围术期临床研究^*[J]. 实用肝脏病杂志, 2019, 22(2): 272-275.
[15]	赵西太综述,聂青和审校. 循环microRNA早期诊断肝细胞癌研究现状及方法学探讨[J]. 实用肝脏病杂志, 2019, 22(2): 297-300.