人类白细胞抗原-DQB1基因多态性与家族性乙肝原发性肝癌相关性研究

发布时间：2018-03-30 16:09

本文选题：肝炎　切入点：乙型　出处：《山西医科大学》2014年硕士论文

【摘要】：目的（一）探讨家族性乙型肝炎的感染模式、临床转归以及影响预后的相关因素。（二）探讨家族性乙肝原发性肝癌与人类白细胞抗原（HLA)-DQB1等位基因多态性的相关性。方法（一）采用回顾性流行病学研究方法，对家族性乙型肝炎的患者及其直系亲属进行当面或电话随访，了解其HBV的感染、治疗及进展等情况，并对相关指标进行统计分析。（二）分组：乙肝相关性原发性肝癌118例、家族性乙肝原发性肝癌39例，以山西地区正常人群（CON）HLA-DQB1的频率分布作为正常总体对照；根据HBV-DNA定量检测结果将乙肝相关性原发性肝癌分为两组：HBV-DNA阳性组60例（HBV-DNA≥1×103copy/ml）和HBV-DNA阴性组58例（HBV-DNA㩳1×103copy/ml）。采用聚合酶链反应-直接碱基序列分析基因分型（PCR-SBT）技术，对乙肝相关性原发性肝癌患者的HLA-DQB1等位基因多态性进行检测，并对实验结果进行统计学分析。结果（一）临床流调279例HBV感染者中，母亲单方为HBV感染者占46.6%，母亲以自然分娩为主，绝大多数没有采取阻断措施。随着患者年龄的增长，其子女HBV的感染率增加，尤其以40岁以上的患者为著（χ2=17.424，P0.001；χ2=39.545，P0.001）。抗病毒与未抗病毒的患者的疾病进展率差异有统计学意义（χ2=5.338，P0.05），前者明显低于后者。终末期肝病—肝硬化、肝癌患者中，HBeAg阳性比例减少，HBV-DNA阳性比例增加。（二）（1）HLA-DQB1*0202、*0301等位基因在乙肝相关性原发性组频率（11.8%、29.3%）高于正常人群组频率（7.6%、21.1%)，差异有统计学意义（u值分别为2.43、3.09，P0.05），RR分别为1.581、1.477。（2）家族性乙肝原发性肝癌组的HLA-DQB1*0202、*0301等位基因频率（14.1%、29.5%）高于正常人群的基因频率（7.6%、21.1%），差异有统计学意义（u值分别为3.76、3.16，P0.05），RR分别为1.928、1.495；HLA-DQB1*0302等位基因的基因频率（0%）低于正常人群的基因频率（5.7%），差异有统计学意义（u值分别为3.77，P0.05），RR为0。（3）对乙肝相关性原发性肝癌中不同HBV-DNA含量进行比较显示，HLA-DQB1*0301等位基因在HBV-DNA阳性组的频率(35.0%)高于HBV-DNA阴性组的频率(23.3%)，HLA-DQB1*0302等位基因在HBV-DNA阳性组的频率(1.7%)低于HBV-DNA阴性组的频率(6.9%)，，差异有统计学意义（χ2=5.543，P=0.0019㩳0.05；χ2=4.604，P=0.0032㩳0.05），RR分别为1.775、0.229。结论（一）母婴传播是导致乙型肝炎家族聚集性的重要原因，没有采取母婴阻断可能是其高感染率的主要原因；抗病毒治疗可以延缓疾病的进展、有效改善患者的预后；原发性肝癌患者中，HBeAg和HBV-DNA阴性的HBV感染者占相当比例，应关注以HBeAg阴性、HBV-DNA阴性感染为主的终末期肝病。（二）HLA-DQB1*0202、*0301等位基因可能是乙肝相关性原发性肝癌的易感基因，可能也是家族性乙肝原发性肝癌的易感基因，HLA-DQB1*0302等位基因可能是家族性乙肝原发性肝癌的抗性基因。HLA-DQB1*0301等位基因可能与肝细胞HBV-DNA复制有关，从而可能导致肝癌，而HLA-DQB1*0302等位基因可能会抑制HBV-DNA的复制从而减少肝癌的发生。
[Abstract]:objective
(1) to investigate the infection patterns, clinical outcomes and factors affecting the prognosis of familial hepatitis B.
(two) to investigate the correlation between HBCC and human leukocyte antigen (HLA) -DQB1 allele polymorphism.
Method
(1) using retrospective epidemiological study method, we visited the family members of hepatitis B and their immediate relatives in person or telephone to understand the infection, treatment and progress of HBV, and analyzed the related indicators.
(two) groups: HBV associated hepatocellular carcinoma 118 cases of familial hepatitis B, 39 cases of primary hepatocellular carcinoma with normal population of Shanxi (CON) the frequency distribution of HLA-DQB1 as normal overall control; according to the quantitative detection of HBV-DNA will result in HBV related hepatocellular carcinoma were divided into two groups: HBV-DNA positive group (60 cases HBV-DNA = 1 * 103copy/ml) and HBV-DNA negative group 58 cases (HBV-DNA? 1 x 103copy/ml). By polymerase chain reaction and direct sequence analysis of genotype (PCR-SBT) technique of HBV related primary hepatic carcinoma patients were detected HLA-DQB1 gene polymorphism, and the results were statistically analyzed.
Result
(a) clinical epidemiological survey of 279 cases of HBV infection in HBV infected mothers alone accounted for 46.6% of mothers with natural childbirth, most did not take measures to block. With the growth of the age, the children HBV infection rate increased, especially in patients over the age of 40 to 17.424 (x 2=, P0.001; x 2=39.545, P0.001). With the progress of antiviral but no antiviral disease rate difference was statistically significant (2=5.338, P0.05), significantly lower than the latter. The end-stage liver disease, liver cirrhosis, hepatocellular carcinoma patients, the positive rate of HBeAg decreased, the positive rate of HBV-DNA increased.
(two) (1) HLA-DQB1*0202, *0301 alleles in the frequency of hepatitis B related primary group (11.8%, 29.3%) were higher than those in the normal group (7.6%, 21.1%), the difference was statistically significant (U value was 2.43,3.09, P0.05), RR was 1.581,1.477. respectively.
(2) familial hepatitis B HCC group HLA-DQB1*0202, *0301 allele frequency (14.1%, 29.5%) gene frequency is higher than the normal population (7.6%, 21.1%), the difference was statistically significant (U = 3.76,3.16, P0.05, RR) were 1.928,1.495; gene frequency of HLA-DQB1* allele (0302 0%) below the gene frequency of normal population (5.7%), the difference was statistically significant (U = 3.77, P0.05), RR 0.
(3) of hepatitis B virus associated primary hepatocellular carcinoma with different HBV-DNA content in comparison showed that HLA-DQB1*0301 allele frequency in the HBV-DNA positive group (35%) was higher than that of HBV-DNA negative group (23.3%), the frequency of HLA-DQB1*0302 allele frequency in the HBV-DNA positive group (1.7%) than the HBV-DNA negative group (6.9%), frequency the difference was statistically significant (x 2=5.543, P=0.0019 x 2=4.604, 0.05?; P=0.0032? 0.05), RR 1.775,0.229. respectively.
conclusion
(a) is an important cause of maternal infant transmission of hepatitis B family aggregation, not taken PMTCT may be the main reason of high infection rate; antiviral therapy can delay the progress of disease, improve the prognosis of patients with primary liver cancer; patients, HBeAg and HBV-DNA negative HBV infection should be accounted for a considerable proportion. Pay attention to HBeAg negative, HBV-DNA negative infection of end-stage liver disease.
(two) HLA-DQB1*0202, *0301 allele may be a susceptibility of HBV related hepatocellular carcinoma gene, may also be susceptible to familial hepatitis B primary liver cancer gene, the HLA-DQB1*0302 allele may be a familial hepatitis B primary liver cancer resistance gene.HLA-DQB1*0301 may be associated with liver cell replication of HBV-DNA. Which may lead to liver cancer, and HLA-DQB1*0302 allele may inhibit the replication of HBV-DNA so as to reduce the occurrence of liver cancer.

【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R735.7;R512.62

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