KIR-HLA基因多态性与散发性急性戊型肝炎的关系

陈冲; 章树业; 荀静娜; 张玉玲; 李微霞; 卢川; 陈良

doi:10.3969/j.issn.1001-5256.2017.03.013

KIR-HLA基因多态性与散发性急性戊型肝炎的关系

DOI: 10.3969/j.issn.1001-5256.2017.03.013

1. 温州医科大学
2. 复旦大学附属上海市公共卫生临床中心

基金项目:

国家重点基础研究发展计划“973计划”(2015CB554303)；上海申康医院发展中心市级医院新兴前沿技术联合攻关项目(SHDC12015129)；上海市科委“科技创新行动计划”医学与农业领域重点项目(13401902100)；

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中图分类号: R512.6
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出版历程
- 出版日期: 2017-03-20

Association between killer cell immunoglobulin- like receptor/human leukocyte antigen gene polymorphisms and sporadic acute hepatitis E

Wenzhou Medical University

Research funding:

摘要

摘要: 目的探讨杀伤性免疫球蛋白样受体（KIR）及其配体人类白细胞抗原（HLA）的基因多态性与散发性急性戊型肝炎（AHE）的相关性。方法收集2015年8月-2016年9月期间于复旦大学附属公共卫生临床中心肝炎一科住院的AHE患者42例,另招募健康受试者30例作为对照组。提取入组对象外周血基因组DNA,采用序列特异性引物PCR法扩增KIR基因,并利用Sanger测序法对HLA进行基因分型,分析KIR-HLA分布与散发性AHE的关系。计数资料组间比较采用χ2检验。结果两组均可检测到16种KIR基因（包括抑制型受体基因2DL1-3、2DL5、3DL1-3,激活型受体基因2DS1-5、3DS1,较特殊的抑制型/激活型受体基因2DL4,内参基因DRB1及假基因2DP1）,同时HLA-B（包括HLA-Bw4、HLA-Bw6、HLA-Bw4/Bw6）、HLA-C（包括HLA-C1/C1、HLA-C1/C2、HLA-C2/C2）亦可检测。AHE患者中抑制型基因KIR 2DL3/2DL5/3DL2/3DL3出现的频率显著低于对照组（64.3%vs 93.3%,P<0.05;23.8%...
- 肝炎,戊型 /
- 多态性,单核苷酸 /
- 受体,自然杀伤细胞 /
- HLA抗原 /
- 基因型
Abstract: Objective To investigate the association between killer cell immunoglobulin-like receptor (KIR) /human leukocyte antigen (HLA) gene polymorphisms and sporadic acute hepatitis E (AHE) .Methods A total of 42 AHE patients who were hospitalized in First Department of Hepatitis, Public Health Clinical Center Affiliated to Fudan University, from August 2015 to September 2016 were enrolled, and 30 healthy subjects were enrolled as control group.Genomic DNA was extracted from the peripheral blood, and PCR/sequence specific primer was used for the amplification of KIR gene.Sanger sequencing was used to determine the genotype of HLA, and the association between KIR-HLA distribution and sporadic AHE was analyzed.The chi-square test was used for comparison of categorical data between groups.Results A total of 16 KIR genes were detected in each group, including inhibitory receptor genes 2DL1-3, 2DL5, and 3DL1-3, activating receptor genes 2DS1-5 and 3DS1, the special inhibitory/activating receptor gene 2DL4, internal reference gene DRB1, and pseudogene 2DP1, as well as HLA-B (including HLA-Bw4, HLA-Bw6, and HLA-Bw4/Bw6) and HLA-C (including HLA-C1/C1, HLA-C1/C2, and HLA-C2/C2) , were also detected.Compared with the control group, the AHE group had significantly lower frequencies of inhibitory genes KIR 2DL3 (64.3% vs 93.3%, P<0.05) , 2DL5 (23.8% vs 56.7%, P<0.05) , 3DL2 (71.4% vs 100%, P<0.05) , and 3DL3 (69.0% vs 100%, P<0.05) , significantly lower frequencies of HLA-C1C2 (19.0% vs 40.0%, P<0.05) and 3DL1/HLA-Bw4 (45.2% vs 73.3%, P<0.05) , and a significantly higher frequency of HLA-C1/C1 gene (71.4% vs 46.7%, P<0.05) .Conclusion The difference in the distribution of inhibitory genes KIR 2DL3, 2DL5, 3DL2, and 3DL3, HLA-C1C1/C1C2, and 3DL1/HLA-Bw4 may be associated with sporadic AHE caused by hepatitis E virus infection.
- hepatitis E /
- polymorphism /
- single nucleotide /
- receptors /
- natural killer cell

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参考文献(16)

[1]KAMAR N, BENDALL R, LEGRAND-ABRAVANEL F, et al Hepatitis E[J].Lancet, 2012, 379 (9835) :2477-2488.

[2]AGGARWAL R.Hepatitis E:epidemiology and natural history[J].J Clin Exp Hepatol, 2013, 3 (2) :125-133.

[3]ZHU FC, HUANG SJ, WU T, et al.Epidemiology of zoonotic hepatitis E:a community-based surveillance study in a rural population in China[J].PLoS One, 2014, 9 (1) :e87154.

[4]TRINCHIERI G.Biology of natural killer cells[J].Adv Immunol, 1989, 47:187-376.

[5]PARHAM P, NORMAN P J, ABI-RACHED L, et al.Humanspecific evolution of killer cell immunoglobulin-like receptor recognition of major histocompatibility complex classⅠmolecules[J].Philos Trans R Soc Lond B Biol Sci, 2012, 367 (1590) :800-811.

[6]JAMIL KM, KHAKOO SI.KIR/HLA interactions and pathogen immunity[J].J Biomed Biotechnol, 2011, 2011:298348.

[7]KULKARNI S, MARTIN MP, CARRINGTON M.KIR genotyping by multiplex PCR-SSP[J].Methods Mol Biol, 2010, 612:365-375.

[8]PARHAM P, MOFFETT A.Variable NK cell receptors and their MHCclassⅠligands in immunity, reproduction and human evolution[J].Nat Rev Immunol, 2013, 13 (2) :133-144.

[9]SIPS M, LIU Q, DRAGHI M, et al.HLA-C levels impact natural killer cell subset distribution and function[J].Hum Immunol, 2016, 77 (12) :1147-1153.

[10]KHAKOO SI, THIO CL, MARTIN MP, et al.HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection[J].Science, 2004, 305 (5685) :872-874.

[11]AHLENSTIEL G, MARTIN M P, GAO X, et al.Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses[J].J Clin Invest, 2008, 118 (3) :1017-1026.

[12]O'CONNOR GM, VIVIAN JP, WIDJAJA JM, et al.Mutational and structural analysis of KIR3DL1 reveals a lineage-defining allotypic dimorphism that impacts both HLA and peptide sensitivity[J].JImmunol, 2014, 192 (6) :2875-2884.

[13]BOUDREAU JE, MULROONEY TJ, le LUDUEC JB, et al.KIR3 DL1 and HLA-B Density and Binding Calibrate NK Education and Response to HIV[J].J Immunol, 2016, 196 (8) :3398-3410.

[14]YUSA S, CATINA TL, CAMPBELL KS.KIR2DL5 can inhibit human NK cell activation via recruitment of Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) [J].J Immunol, 2004, 172 (12) :7385-7392.

[15]CAULI A, PIGA M, DESSOLE G, et al.Killer-cell immunoglobulin-like receptors (KIR) and HLA-classⅠheavy chains in ankylosing spondylitis[J].Drug Dev Res, 2014, 75 (Suppl 1) :s15-s19.

[16]ZHOU L, LI XY, HUANG YH.Regulatory effect of interleukin-10 on natural killer cells in patients with chronic hepatitis B[J].J Clin Hepatol, 2016, 32 (8) :1600-1603. (in Chinese) 周亮, 李小燕, 黄月华.白细胞介素10对慢性乙型肝炎患者自然杀伤细胞的调控作用[J].临床肝胆病杂志, 2016, 32 (8) :1600-1603.

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