甘肃地区乙型肝炎病毒基因型和基因变异与原发性肝癌的关系

Study on the relationship between hepatocellular carcinoma and hepatitis B virus genotypes or viral nnttations

目的探讨甘肃地区HBV感染人群的乙型肝炎病毒核心基因启动子（BCP）以及前C区变异情况，分析HBV变异、HBV基因型与原发性肝细胞癌（HCC）的关系。方法对甘肃第二人民医院的62例HCC、70例乙型肝炎肝硬化（IJC）及90例慢性乙型肝炎（CHB）患者的血清进行分析。采用限制性片段长度多态性聚合酶链反应（PCR-RrLP）法确定基因型，基因亚型的确定采用PCR-RFLP法或者核苷酸序列分析，前C基因区、BCP区变异使用PCR或扩增产物直接测序法。结果甘肃地区HCC患者以C基因型为主（70．97％）。前C区和BCP在HCC、LC、CHB组的变异率分别为59．68％、31．43％、16．67％和74．19％、51．43％、37．78％，组间均具有统计学差异（x^2=30．73、19．54，P均〈0．01）。前C区和BCP变异在HBVC1、C2、Ba3个基因亚型间比较，差异均具有统计学意义（x^2=7．93，P〈0．05；x^2=22．38，P〈0．01），且在C1亚型中的分布均最高（44．32％和69．32％）。结论甘肃地区HBV感染人群前C区和BCP变异发生率随着病程进展而递增；前C区、BCP变异较易发生在C1亚型中。HBVC基因型、前C区及BCP变异是HCC发生的密切相关因素。

Objective To explore the ratios of HBV basic core promoter （BCP） ,HBV pre-C region（PC） muta- tiom in the people with HBV infection in Gansu Province and analysis the correlation between hepatocellular carcinoma （HCC） and HBV genotypes or HBV mutations. Methods Serum samples of 62 patients with HCC, 70 patients with Liv- er cirrhosis（LC） and 90 patients with chronic hepatitis B（CHB） from the Second Hospital of Gansu Province were tested respectively. HBV genotypes were determined by PCR restriction fragment length polymorphism （PCR-RFLP）. BCP and PC mutation were determined by PCR or direct sequencing of amplified products, and subgenotypes were determined by nucleotide sequence analysis or PCR-RFLP. Resttlts The results showed that the most cormnon genotype was C in the HCC patients of Gansu （70.97%）. In the serum samples of HCC,LC and CHB patients, the mutation ratios of PC were 59.68% ,31.43% and 16.67% ,respectively,and the mutation ratios of BCP were 74.19% ,51.43% and 37.78%, re- spectively. The ratios of BCP and PC mutation in three groups were significantly different（x^2 = 30.73,19.54, P all 〈 0.01）. The ratios of BCP and PC mutation in HBV subgenotype C1, C2, Ba were significantly different（ x^2 = 7.93, P 〈 0.05; x^2 = 22.38, P 〈 0.01 ） and the mutation rates of those in subgenotype C1 were the highest （44.32% and 69.32 % ）. Conclusions With the progression of HBV infection, the ratios of BCP and PC mutation are increasing. The BCP and PC mutations are always associated with the HBV subgenotype C1. It suggests that BCP mutation, PC mutation and the genotype C have high correlation with HCC development.