摘要
目的探讨慢性HBV感染者和肝细胞癌患者细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)和T细胞免疫球蛋白及黏蛋白分子-3(T cell immunoglobulin and mucin domain-3,TIM-3)的基因多态性分布,以及二者的联合作用。方法通过病例对照研究方法,提取439例慢性HBV感染者(无症状携带者48例,慢性肝炎154例,肝硬化134例和肝癌103例)和220例健康对照者的基因组DNA,限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测所有患者DNA的CTLA-4+49 A/G和TIM-3-1516 G/T基因型分布频率,采用χ^(2)检验分析基因型频率、等位基因频率在HBV感染组与对照组的分布情况以及在肝癌组与非肝癌组的分布情况。结果HBV感染组的CTLA-4+49含A基因型(GA+AA)频率高于对照组(P<0.001,OR=1.924)。HBV感染组的TIM-3-1516含T基因型(GT+TT)频率高于对照组(P=0.002,OR=2.263)。CTLA-4+49 GG/TIM-3-1516 GG基因型组合在HBV感染组中的分布频率低于对照组(P<0.001,OR=0.242)。非肝癌组(无症状携带者、慢性肝炎和肝硬化患者)的CTLA-4+49 GA和AA基因型频率高于肝癌组(分别为P<0.001,OR=2.433和P=0.003,OR=2.798)。非肝癌组的TIM-3-1516 GG基因型频率高于肝癌组(P=0.042,OR=1.725)。CTLA-4+49 GA/TIM-3-1516 GG和CTLA-4+49 AA/TIM-3-1516 GG基因型组合在非肝癌组的分布频率高于肝癌组(分别为P=0.001,OR=3.728和P=0.003,OR=4.032)。结论CTLA-4+49含A基因型和TIM-3-1516含T基因型可能是慢性HBV感染的危险因素,基因型组合增加了慢性HBV感染的发病风险。CTLA-4+49 GG基因型和TIM-3-1516 GT+TT基因型可能与HCC发生相关,基因型组合也增加了HCC发生的风险。CTLA-4和TIM-3基因多态性可能各自并联合地增加慢性HBV感染和肝细胞癌的风险。
Objective To investigate the distribution of CTLA-4 and TIM-3 gene polymorphisms and their interaction in patients with chronic HBV infection and hepatocellular carcinoma.Methods Genomic DNA was extracted from 439 patients with chronic HBV infection(48 asymptomatic carriers,154 chronic hepatitis,134 cirrhosis and 103 liver cancer)and 220 healthy controls for a case-control study.The frequencies of CTLA-4+49 A/G and TIM-3-1516 G/T genotypes were detected by PCR-RFLP.The genotype frequency and the allele frequency were analyzed by χ^(2) test between HBV infection group and healthy control group,and between liver cancer group and non-liver cancer group.Results The frequency of CTLA-4+49 A-containing genotype(GA+AA)was higher in HBV infection group than in control group(P<0.001,OR=1.924).The frequency of TIM-3-1516 T-containing genotype(GT+TT)was higher in HBV infection group than in control group(P=0.002,OR=2.263).The frequency of genotype combination CTLA-4+49 GG/TIM-3-1516 GG was lower in HBV infection group than in control group(P<0.001,OR=0.242).The frequencies of CTLA-4+49 GA and AA genotype were higher in non-HCC group(ASC,CH,and LC patients)than in HCC group,respectively(P<0.001,OR=2.433;P=0.003,OR=2.798).The frequency of TIM-3-1516 GG genotype was higher in non-HCC group than in HCC group(P=0.042,OR=1.725).The frequencies of genotype combination CTLA-4+49 GA/TIM-3-1516 GG and CTLA-4+49 AA/TIM-3-1516 GG were higher in non-HCC group than in HCC group,respectively(P=0.001,OR=3.728;P=0.003,OR=4.032).Conclusion CTLA-4+49 containing A genotype and TIM-3-1516 containing T genotype may be risk factors for chronic HBV infection,and the combination of genotype increases the risk of chronic HBV infection.CTLA-4+49 GG genotype and TIM-3-1516 GT+TT genotype may be associated with HCC development,and the combination of genotype also increases the risk of HCC development.Single or combination of CTLA-4 and TIM-3 gene polymorphisms may increase the risk of chronic HBV infection and hepatocellular carcinoma.
作者
张国妤
卢乐
黎巧信
陆宏伟
ZHANG Guoyu;LU Le;LI Qiaoxin;LU Hongwei(Department of Infectious Diseases,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;Department of General Surgery,Second Affiliated Hospital of Xi’an Jiaotong University)
出处
《山西医科大学学报》
CAS
2022年第6期746-753,共8页
Journal of Shanxi Medical University
基金
国家自然科学基金资助项目(81600474)
陕西省自然科学基金项目(2018JM7034,2017JQ8014)。
关键词
乙型肝炎病毒感染
CTLA-4
TIM-3
基因多态性
肝细胞癌
hepatitis B virus infection
cytotoxic T lymphocyte associated antigen-4
T cell immunoglobulin and mucin domain-3
gene polymorphism
hepatocellular carcinoma
