血清IL-17水平及其基因多态性与HBV感染临床转归之间的关系研究*

doi:10.3969/j.issn.1672-5069.2018.06.008

摘要/Abstract

摘要： 目的探讨血清白介素（IL）-17水平和IL-17-197A/G基因单核苷酸多态性与乙型肝炎病毒（HBV）感染临床转归之间的关系。方法 2015年3月~2017年8月在我院就诊的乙型肝炎肝硬化40例,慢性乙型肝炎120例,无症状慢性HBV携带者60例和自限性HBV感染者80例。采用酶联免疫吸附试验检测血清IL-17水平,使用全自动生化仪检测血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBIL）水平,采用多聚酶链反应结合荧光探针DNA扩增技术检测血清HBV DNA载量,使用单核苷酸检测试剂盒检测IL-17-197A/G基因单核苷酸多态性。结果乙型肝炎肝硬化组血清IL-17水平显著高于慢性乙型肝炎组、无症状慢性HBV携带者组和自限性HBV感染组（F_3,296=102.8,P均<0.05）;慢性乙型肝炎组血清IL-17水平显著高于无症状慢性HBV携带者组和自限性HBV感染组（P均<0.05）;在乙型肝炎肝硬化组,血清高HBV DNA载量组（>1×10⁵ copies/mL）血清IL-7水平更高（t=5.1,P<0.05）,血清ALT>40 U/L组血清IL-7水平更高（t=10.7,P<0.05）;在慢性乙型肝炎组和乙型肝炎肝硬化组,血清AST>40 U/L组血清IL-7水平更高（t=24.5,P<0.05;t=22.4,P<0.05）,血清TBIL>20 μmol/L组血清IL-7水平更高（t=7.3,P<0.05;t=12.8,P<0.05）;肝硬化患者IL-17-197 AA、AG和GG基因型分别为75.0%、10.0%和15.0%,等位基因A分布频率为57.5%,G分布频率为42.5%,而慢性乙型肝炎患者则分别为25.8%、16.7%、57.5%和34.2%、65.8%,组间差异显著（P<0.05）,乙型肝炎肝硬化组以IL-17-197 AA基因型和A等位基因分布频率为主,慢性乙型肝炎组以GG基因型和G等位基因分布频率为主,HBV携带者组以AA基因型和A等位基因分布为主,自限性HBV感染者以GG基因型和G等位基因分布为主。结论宿主免疫水平和遗传背景的相互作用决定了HBV感染的临床转归,IL-17在乙型肝炎病毒感染慢性化进程中发挥了重要作用。IL-17-197A/G位点的AA基因型和A等位基因可能是HBV易感的宿主基因,增加了HBV感染的不良转归。

关键词: 肝硬化, 乙型肝炎, 白细胞介素-17, 基因多态性

Abstract: Objective To investigate serum IL-17 and its gene polymorphism in clinical outcomes of individuals with chronic hepatitis B viral infection. Methods 40 patients with hepatitis B liver cirrhosis, 120 patients with chronic hepatitis B,60 patients with asymptomatic HBV carriers and 80 individuals with self-limited HBV infection were rucruited in this study between March 2015 and August 2017. Serum IL-17 levels were detected by ELISA,serum alanine aminotransferase（ALT）,aspartate aminotransferase（AST） and total bilirubin （TBIL） levels were detected by automatic biochemical analyzer. Serum HBV DNA load was detected by polymerase chain reaction with fluorescent probe,and the single nucleotide detection kit was used for polymorphism detection. Results Serum level of IL-17 in patients with hepatitis B liver cirrhosis was higher than in patients with chronic hepatitis B,asymptomatic HBV carrier or self-limited HBV infection（F_3,296=102.8,P<0.05）; serum IL-17 level in patients with chronic hepatitis B was significantly higher than in asymptomatic HBV carrier or self-limited HBV infection（P<0.05）;in patients with hepatitis B liver cirrhosis,serum IL-17 level increased in those with higher serum HBV DNA load（t=5.1,P<0.05） and high ALT level（t=10.7,P<0.05）;in both patients with hepatitis B liver cirrhosis and chronic hepatitis B,serum IL-17 levels increased in those with higher serum ALT levels（t=24.5,P<0.05;t=22.4,P<0.05）and with higher serum bilirubin levels（t=7.3,P<0.05;t=12.8,P<0.05）;the frequency of IL-17-197 AA,AG and GG distribution in patients with liver cirrhosis were 75.0%,10.0% and 15.0%,and allele A distribution frequency was 57.5%,G distribution frequency was 42.5%,while in patients with chronic hepatitis B were 25.8%,16.7%,57.5% and 34.2%,65.8%,respectively,significantly different between the two groups （P<0.05）;the priority frequencies in patients with liver cirrhosis were IL-17-197 AA genotype and A allele,the priority frequencies in patients with chronic hepatitis B were GG genotype and G allele,the priority frequencies in asymptomatic HBV carrier were AA genotype and A allele,and the priority frequencies in self-limited individuals were GG genotype and G allele. Conclusion The host immunity and genetic background determine the outcomes of HBV infection and serum IL-17 plays an important role in the process of chronic hepatitis B virus infection. The AA genotypes and A alleles of IL-17-197A/G might be the HBV susceptible host genes,which increase the adverse outcome of HBV infection.

Key words: Liver cirrhosis, Hepatitis B, Interleukin -17, Gene polymorphism

何胜, 张震. 血清IL-17水平及其基因多态性与HBV感染临床转归之间的关系研究^*[J]. 实用肝脏病杂志, 2018, 21(6): 855-858.

He Sheng, Zhang Zhen.. What roles of serum IL-17 gene polymorphism in individuals with chronic hepatitis B viral infection[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(6): 855-858.

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血清IL-17水平及其基因多态性与HBV感染临床转归之间的关系研究^*

What roles of serum IL-17 gene polymorphism in individuals with chronic hepatitis B viral infection

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