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Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Epidemiological studies also provide a lot of data to prove a causal association of HBV infection and HCC. Since the advent of PCR amplified viral DNA, HBV genome sequence heterogeneity in the pathogenesis and the role of viral protein expression research has become the focus of the study of hepadnavirus. HBV gene mutant selection in the process of chronic infection or the development of liver disease, the most important of immune escape mutant S region of the \mutations in other regions there are few studies. Our country is a high HBV endemic areas, the epidemic strain low endemic areas such as Europe, America and Japan, the major genotype B-type and C-type. Existing HBV standard sequence abroad epidemic strains sequence. Gene library and the standard sequence of HBV epidemic strain, which is a the HBV mutation research work. HBV gene locus mutation and HBV-related disease association analysis may prompt some variation of the gene locus may be associated with clinical hepatitis B-related disease. Purposes of hepatitis B e antigen (HBeAg)-positive asymptomatic surface antigen (HBsAg) carriers (ASCs) B2, and C2 genetic subtype Complete genome sequence determination, initially established based on the epidemic strains sequence B2, C2 genotype HBV standard sequence. B, type C chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in patients with HBV partial gene sequencing to explore the different genotypes (C genotype) and gene variants with hepatitis B-related liver disease The association of the various disease states. Ordinary and nested polymerase chain reaction (Nest-PCR) method, were amplified by 485 patients with HBeAg-positive B2 and C2 type ASCs full genome sequence, and 81 cases of CHB and 98 cases of LC patients and 135 cases of hepatitis B-positive patients with HCC HBV and sequenced part of the gene sequence. Gene sequence fragment first MEGA5.0 clustal w software sequence alignment and then for each piece of stitching, ASCs spliced ??into a full-length. \As in all of the samples as long as the frequency of each point mutation in each category of disease in the B or C type greater than 10%, i.e. the \Data entry and analysis using the SPSS 16.0 statistical software and of condensed statistical software 10.35, the relationship between the the single factor χ2 test and non-conditional logistic regression model analysis of genotype and mutation sites and their interaction with ASC, CHB, LC and HCC. Image processing software ORIGIN6.0 analysis of the different ages of the various disease states HBV mutation frequency change. Results obtained the ASCs of HBeAg-positive hepatitis B virus B2 and C2 genetic subtype standard sequence, the two genotypes homology of 91.8%. In all samples, compared with the ASCs CHB, LC and HCC patients generally high age, men and C genotype majority (ASCs C genotype ratio of 55.1%, CHB, LC and HCC C genotype proportions were 79.0% , 80.6% and 86.7%, respectively). According to HBV genotype B2 and C2 wild sequence analysis of the 66 hot spots of the relevant regional variation, higher than most of the sites of mutation frequency C-type B-type. C genotype, the ASC as the control group, A1206C is a risk factor of the LC; C873T, G1229A, A1314G, T1344C, T1353C, A1359G, C1362T, T1497C, C1504T, T1508A, G1512A, A1727T, A2574G is a risk factor for HCC; C1338T , G1386A, T1464C, T1500C, T1544A, G1613A, C1653T, T1674C, G1719T, A1727G, G2699C LC, HCC risk factors; G915A, A993G, A1053G, C1218T, A1221T, G1230C, T2441C, G2699A CHB, LC, HCC's risk factors. C genotype ASC as the control group, T929A CHB protective factors; A1329C LC protective factors; T1078G, A1329C, C1505T, A1574T protective factors for HCC; T796G, A934C, T2465A is CHB, LC protective factors ; T1488C, C1491C LC, HCC protective factors; G834A, G912A, C2456T, A2558G CHB, LC, HCC protective factors. With CHB, A1206C LC risk factors; compared with the LC T796G, G1229A, T1344C, A1359G, T2441C, A2574G HCC risk factors. Compared with the LC, G1230C HCC protective factors. 3 C genotype compared with LC G1229A is a risk factor for HCC in HBeAg-positive patients T796G, G1230C HCC protective factors HBeAg positive than negative LC patients occurred T796G G1229A easier HCC occurred G1230C not easy HCC; compared with the LC, is a risk factor for HCC in HBeAg-negative patients with A2574G HBeAg negative than positive LC patients occurred A2574G easier HCC; compared with CHB, LC risk factors in patients with HBeAg-positive A1206C Description HBeAg positive than negative CHB patients occurred A1206C easier HCC. 4. Univariate and multivariate regression analysis showed that the T796G, C1218T, A1221T, G1229A, T1344C, A2574G independent risk factors of HCC; G912A, G1230C, C2456T protective factors for HCC. HCC and LC 8 sites and did not increase with increasing age, the mutation frequency; ASCs, the mutation frequency increases with age changes. T796G, G912A and C2456T ASC HCC, LC and CHB group was significantly higher than average mutation frequency. C1218T, A1221T and G1230C ASC HCC, LC and CHB group was significantly lower than average mutation frequency. G1229A and A2574G, HCC average mutation frequency (49.6%, 38.5%) was significantly higher than the LC, CHB and ASC group (G1229A were 32.9%, 28.1%, 38.6%, A2574G were 15.2%, 15.6%, 21.7%) . 5. Analysis of HCC in patients with lamivudine (LAM) resistance locus YMDD (M204V / I) variability. Experimental samples used are no patients undergoing antiviral therapy, we have detected some HCC samples P (polymerase) gene region of 739 (YVDD) and 741 (YIDD) point mutations, found A739G variation of only 5.81%, G741T variation of only 4.65% to lamivudine therapy five-year resistance rates close to 70%, not taking antiviral natural mutation rate is not high. Conclusion 1, hepatitis B virus B2 and C2 genetic subtype standard sequence heterogeneity was 8.2%. C genotype, HBeAg positive than negative LC patients occurred T796G the G1229A HCC easier, and occurred the G1230C not easy HCC; HBeAg negative than positive LC patients occurred A2574G easier HCC; HBeAg-positive than the negative CHB patients A1206C easier HCC. 3, C1218T, A1221T, G1229A, A2574G is an independent risk or protective factors of HCC.
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