深圳地区乙型肝炎病毒携带者人白细胞抗原C等位基因多态性分布特点
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摘要
背景:目前,较多文献是研究乙型肝炎病毒与人白细胞抗原(human leukocyte antigen,HLA)A、B、DR之间的关系,较少文献报道乙型肝炎病毒与HLA-C的相关性,可能与HLA基因型检测方法的发展有关系。目的:研究深圳地区乙型肝炎病毒携带者HLA-C等位基因多态性分布特征。方法:应用聚合酶链反应-直接测序分型法分别对186名深圳地区健康人群(对照组)和122名乙型肝炎病毒携带者HLA-C基因进行基因分型。结果与结论:在对照组中检出的HLA-C等位基因有24种,其中HLA-C*01:02、07:02、03:04以及08:01最为常见;携带组检出HLA-C等位基因有18种,常见等位基因有HLA-C*07:02、01:02、03:04、08:01。携带组中未检出基因HLA-C*12:02,对照组HLA-C*12:02检出率显著高于携带组,提示深圳地区乙型肝炎病毒携带者HLA-C等位基因频率分布与对照组比较同样具有高度的遗传多态性。HLA-C*12:02基因可能与深圳地区感染乙型肝炎病毒的机会呈负相关性。
BACKGROUND: Due to the development of human leukocyte antigen(HLA) typing techniques, there are a large number of studies reporting the relationship between hepatitis B virus(HBV) and HLA-A,-B, and-DR,but little is reported on the relationship between HBV and HLA-C. OBJECTIVE: To analyze the polymorphism of HLA-C of HBV carriers in Shenzhen. METHODS: PCR-based typing method was used to analyze the polymorphism of HLA-C locus alleles of 122 HBV carriers and 186 healthy volunteers(control group) in Shenzhen. RESULTS AND CONCLUSION: Twenty-four alleles for the locus HLA-C were detected in the control group, of which HLA-C *01:02, 07:02, 03:04 and 08:01 were the most common. In the HBV carrier group, 18 kinds of HLA-C alleles were detected, including the common alleles HLA-C*07:02, 01:02, 03:04, 08:01. HLA-C*12:02 was not detected in the HBV carries group. The detection rate of HLA-C*12:02 in the control group was significantly higher than that in the HBV carrier group. These results imply that the frequency distribution of HLA-C alleles of HBV carriers in Shenzhen also have a high degree of genetic polymorphism compared with the control group. There may be association between HBV carriers and HLA-C*12:02 alleles. HLA-C*12:02 allele possibly plays a negative role in HBV carriers in Shenzhen.
BACKGROUND: Due to the development of human leukocyte antigen(HLA) typing techniques, there are a large number of studies reporting the relationship between hepatitis B virus(HBV) and HLA-A,-B, and-DR,but little is reported on the relationship between HBV and HLA-C. OBJECTIVE: To analyze the polymorphism of HLA-C of HBV carriers in Shenzhen. METHODS: PCR-based typing method was used to analyze the polymorphism of HLA-C locus alleles of 122 HBV carriers and 186 healthy volunteers(control group) in Shenzhen. RESULTS AND CONCLUSION: Twenty-four alleles for the locus HLA-C were detected in the control group, of which HLA-C *01:02, 07:02, 03:04 and 08:01 were the most common. In the HBV carrier group, 18 kinds of HLA-C alleles were detected, including the common alleles HLA-C*07:02, 01:02, 03:04, 08:01. HLA-C*12:02 was not detected in the HBV carries group. The detection rate of HLA-C*12:02 in the control group was significantly higher than that in the HBV carrier group. These results imply that the frequency distribution of HLA-C alleles of HBV carriers in Shenzhen also have a high degree of genetic polymorphism compared with the control group. There may be association between HBV carriers and HLA-C*12:02 alleles. HLA-C*12:02 allele possibly plays a negative role in HBV carriers in Shenzhen.
引文
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[12]李建忠,李长缨.人群HBV易感性与HLA-Ⅰ、Ⅱ类基因相关性研究.预防医学论坛[J]. 2007,13(4):314-416.
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[14]Mak LY, Wong DK, Seto WK, et al. Hepatitis B core protein as a therapeutic target. Expert Opin Ther Targets. 2017;21(12):1153-1159.
[15]Lutomski CA, Lyktey NA, Zhao Z et al. Hepatitis B Virus Capsid Completion Occurs through Error Correction. J Am Chem Soc. 2017;139(46):16932-16938.
[16]Sch?neweis K, Motter N, Roppert PL, et al. Activity of nucleic acid polymers in rodent models of HBV infection. Antiviral Res. 2018;149:26-33.
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[19]Moretta A, Bottino C, Mingari MC, et al. What is a natural killer cell?Nat Immunol. 2002;3(1):6-8.
[20]K?rre K. NK cells, MHC class I molecules and the missing self. Scand J Immunol. 2002;55(3):221-228.
[21]Shah-Hosseini A, Jafari M, Mohammadi A, et al. The impact of KIR-HLA genotype on hepatitis B virus clearance in Iranian infected individuals. Med Microbiol Immunol. 2017;206(6):463-470.
[22]Nakimuli A, Chazara O, Farrell L, et al. Killer cell immunoglobulin-like receptor(KIR)genes and their HLA-C ligands in a Ugandan population.Immunogenetics. 2013;65(11):765-775.
[23]杨志明.丙型肝炎病毒基因型分布及HLA-Cw基因多态性的关联性分析[J].标记免疫分析与临床,2016,23(12):1395-1398.
[24]孙坚萍,孙焕芹,刘宁,等.中国北京男男同性恋艾滋病感染者HLA分型及与疾病进展分析[J].中国免疫学杂志, 2016,32(8):1183-1186,1191.
[25]田伟,李立新,周劲峰,等.中国南方汉族人群HLA-Cw座位基因多态性分析[J].中华微生物学和免疫学杂志,2001,22(1):99-102.
[26]张洪波,赵钧海,赖江华.新疆维吾尔族HLA-Cw基因座遗传多态性调查[J].遗传,2003,25(5):549-551.
[27]Rasmussen M, Harndahl M, Stryhn A, et al. Uncovering the peptidebinding specificities of HLA-C:a general strategy to determine the specificity of any MHC class I molecule. J Immunol. 2014;193(10):4790-4802.
[28]徐小明,任雨,姚许平,等.供者HLA-Cw和受者KIR基因多态性以及HLACw/KIR组合型对移植肾功能的影响[J].中华移植杂志(电子版),2014,8(1):13-17.
[29]Li J, Han Y, Jin K, et al. Dynamic changes of cytotoxic T lymphocytes(CTLs), natural killer(NK)cells, and natural killer T(NKT)cells in patients with acute hepatitis B infection. Virol J. 2011;8:199.
[30]Blais ME, Dong T, Rowland-Jones S. HLA-C as a mediator of natural killer and T-cell activation:spectator or key player? Immunology. 2011;133(1):1-7.
[31]Israeli M, Roelen DL, Carrington M, et al. Association between CTL Precursor Frequency to HLA-C Mismatches and HLA-C Antigen Cell Surface Expression. Front Immunol. 2014;5:547.
[32]Hundhausen C, Bertoni A, Mak RK, et al. Allele-specific cytokine responses at the HLA-C locus:implications for psoriasis. J Invest Dermatol. 2012;132(3 Pt 1):635-641.
[33]Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006;78(5):827-851.
[34]姚叶萍,曾跃彬,赖小丽.慢性乙型肝炎患者外周血CD8+T淋巴细胞功能的变化[J].肝脏,2015,20(5):356-358.
[35]卢晓敏,王文远,孙成刚.HLA-A基因频率与HBV感染的相关性研究[J].临床肝胆病杂志,2006,22(2):91-92.
[36]蒋雪梅,陈士俊,旭日.山东汉族人乙肝患者与HLA-B基因型的相关性研究[J].山东大学学报:医学版,2005,43(8):737-740.
[37]邢文斌,郭晓楠,徐慧宁.HLA-DRB多态性与HBV感染的相关性研究[J].中华实验和临床感染病杂志:电子版,2015,9(1):65-68.
[38]杨丽,李真,徐菲莉.新疆维吾尔族、汉族慢性乙型肝炎患者HLA-DQA1基因多态性研究[J].重庆医学,2016,45(1):1-4.
[39]Pajewski NM, Parker SD, Poland GA, et al. The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed. Genes Immun. 2011;12(6):457-465.
[40]杜可明,刘达庄.HLA基因分型方法进展[J].中国输血杂志, 2005,18(4):342-345.
[2]Horowitz A, Guethlein LA, Nemat-Gorgani N, et al. Regulation of Adaptive NK Cells and CD8 T Cells by HLA-C Correlates with Allogeneic Hematopoietic Cell Transplantation and with Cytomegalovirus Reactivation. J Immunol. 2015;195(9):4524-4536.
[3]Bettens F, Buhler S, Tiercy JM. Allorecognition of HLA-C Mismatches by CD8+T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities. Front Immunol. 2016;7:584.
[4]Ameres S, Mautner J, Schlott F, et al. Presentation of an immunodominant immediate-early CD8+T cell epitope resists human cytomegalovirus immunoevasion. PLoS Pathog. 2013;9(5):e1003383.
[5]Tan AT, Sodsai P, Chia A, et al. Immunoprevalence and immunodominance of HLA-Cw*0801-restricted T cell response targeting the hepatitis B virus envelope transmembrane region. J Virol. 2014;88(2):1332-1341.
[6]Hu Z, Liu Y, Zhai X, et al. New loci associated with chronic hepatitis B virus infection in Han Chinese. Nat Genet. 2013;45(12):1499-1503.
[7]杨晋,张建琼,沈宇清,等.肝癌细胞中HLA I类重链基因表达与启动子区域甲基化的相关性[J].细胞与分子免疫学杂志, 2007,23(6):582-584.
[8]高素青,邹红岩,程良红,等.应用SBT直接测序分型法研究中国南方汉族人群HLA五个基因座单倍型[J].中华医学遗传学杂志, 2009,26(2):228-232.
[9]黎燕琼.乙型肝炎病毒检测方法的研究现状[J].中外医学研究, 2016,14(8):159-160.
[10]Tan JM, Zhou YC, Tang XD. Tissue Typing Methods and the Clinical Application. Beijing:People’s Medical House,2002:91-93.
[11]Müller CR, Ehninger G, Goldmann SF. Gene and haplotype frequencies for the loci hLA-A, hLA-B, and hLA-DR based on over13,000 german blood donors. Hum Immunol. 2003;64(1):137-151.
[12]李建忠,李长缨.人群HBV易感性与HLA-Ⅰ、Ⅱ类基因相关性研究.预防医学论坛[J]. 2007,13(4):314-416.
[13]Matsubara T, Nishida T, Shimoda A, et al. The combination of anti-HBc and anti-HBs levels is a useful predictor of the development of chemotherapy-induced reactivation in lymphoma patients with resolved HBV infection. Oncol Lett. 2017;14(6):6543-6552.
[14]Mak LY, Wong DK, Seto WK, et al. Hepatitis B core protein as a therapeutic target. Expert Opin Ther Targets. 2017;21(12):1153-1159.
[15]Lutomski CA, Lyktey NA, Zhao Z et al. Hepatitis B Virus Capsid Completion Occurs through Error Correction. J Am Chem Soc. 2017;139(46):16932-16938.
[16]Sch?neweis K, Motter N, Roppert PL, et al. Activity of nucleic acid polymers in rodent models of HBV infection. Antiviral Res. 2018;149:26-33.
[17]Aizawa M, Tsubota A, Fujise K, et al. Clinical course and predictive factors of virological response in long-term lamivudine plus adefovir dipivoxil combination therapy for lamivudine-resistant chronic hepatitis B patients. J Med Virol. 2011;83(6):953-961.
[18]Khomeriki SG, Iakhimchuk GN, Golovanova EV. Clinical significance of intravital morphological investigation of the liver. Ter Arkh. 2011;83(4):30-36.
[19]Moretta A, Bottino C, Mingari MC, et al. What is a natural killer cell?Nat Immunol. 2002;3(1):6-8.
[20]K?rre K. NK cells, MHC class I molecules and the missing self. Scand J Immunol. 2002;55(3):221-228.
[21]Shah-Hosseini A, Jafari M, Mohammadi A, et al. The impact of KIR-HLA genotype on hepatitis B virus clearance in Iranian infected individuals. Med Microbiol Immunol. 2017;206(6):463-470.
[22]Nakimuli A, Chazara O, Farrell L, et al. Killer cell immunoglobulin-like receptor(KIR)genes and their HLA-C ligands in a Ugandan population.Immunogenetics. 2013;65(11):765-775.
[23]杨志明.丙型肝炎病毒基因型分布及HLA-Cw基因多态性的关联性分析[J].标记免疫分析与临床,2016,23(12):1395-1398.
[24]孙坚萍,孙焕芹,刘宁,等.中国北京男男同性恋艾滋病感染者HLA分型及与疾病进展分析[J].中国免疫学杂志, 2016,32(8):1183-1186,1191.
[25]田伟,李立新,周劲峰,等.中国南方汉族人群HLA-Cw座位基因多态性分析[J].中华微生物学和免疫学杂志,2001,22(1):99-102.
[26]张洪波,赵钧海,赖江华.新疆维吾尔族HLA-Cw基因座遗传多态性调查[J].遗传,2003,25(5):549-551.
[27]Rasmussen M, Harndahl M, Stryhn A, et al. Uncovering the peptidebinding specificities of HLA-C:a general strategy to determine the specificity of any MHC class I molecule. J Immunol. 2014;193(10):4790-4802.
[28]徐小明,任雨,姚许平,等.供者HLA-Cw和受者KIR基因多态性以及HLACw/KIR组合型对移植肾功能的影响[J].中华移植杂志(电子版),2014,8(1):13-17.
[29]Li J, Han Y, Jin K, et al. Dynamic changes of cytotoxic T lymphocytes(CTLs), natural killer(NK)cells, and natural killer T(NKT)cells in patients with acute hepatitis B infection. Virol J. 2011;8:199.
[30]Blais ME, Dong T, Rowland-Jones S. HLA-C as a mediator of natural killer and T-cell activation:spectator or key player? Immunology. 2011;133(1):1-7.
[31]Israeli M, Roelen DL, Carrington M, et al. Association between CTL Precursor Frequency to HLA-C Mismatches and HLA-C Antigen Cell Surface Expression. Front Immunol. 2014;5:547.
[32]Hundhausen C, Bertoni A, Mak RK, et al. Allele-specific cytokine responses at the HLA-C locus:implications for psoriasis. J Invest Dermatol. 2012;132(3 Pt 1):635-641.
[33]Nair RP, Stuart PE, Nistor I, et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet. 2006;78(5):827-851.
[34]姚叶萍,曾跃彬,赖小丽.慢性乙型肝炎患者外周血CD8+T淋巴细胞功能的变化[J].肝脏,2015,20(5):356-358.
[35]卢晓敏,王文远,孙成刚.HLA-A基因频率与HBV感染的相关性研究[J].临床肝胆病杂志,2006,22(2):91-92.
[36]蒋雪梅,陈士俊,旭日.山东汉族人乙肝患者与HLA-B基因型的相关性研究[J].山东大学学报:医学版,2005,43(8):737-740.
[37]邢文斌,郭晓楠,徐慧宁.HLA-DRB多态性与HBV感染的相关性研究[J].中华实验和临床感染病杂志:电子版,2015,9(1):65-68.
[38]杨丽,李真,徐菲莉.新疆维吾尔族、汉族慢性乙型肝炎患者HLA-DQA1基因多态性研究[J].重庆医学,2016,45(1):1-4.
[39]Pajewski NM, Parker SD, Poland GA, et al. The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed. Genes Immun. 2011;12(6):457-465.
[40]杜可明,刘达庄.HLA基因分型方法进展[J].中国输血杂志, 2005,18(4):342-345.