Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression
<p>Abstract</p> <p>Background</p> <p>Mutations in the basic core promoter (BCP) and its adjacent precore (preC) region in HBV genome are common in chronic hepatitis B patients. However, the patterns of mutation combinations in these two regions during chronic infection...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-09-01
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| Series: | BMC Infectious Diseases |
| Online Access: | http://www.biomedcentral.com/1471-2334/10/271 |
| _version_ | 1818145592982896640 |
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| author | Zhang Dake Ma Sufang Zhang Xin Zhao Hanqing Ding Huiguo Zeng Changqing |
| author_facet | Zhang Dake Ma Sufang Zhang Xin Zhao Hanqing Ding Huiguo Zeng Changqing |
| author_sort | Zhang Dake |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mutations in the basic core promoter (BCP) and its adjacent precore (preC) region in HBV genome are common in chronic hepatitis B patients. However, the patterns of mutation combinations in these two regions during chronic infection are less understood. This study focused on single base mutations in BCP and preC region and the multi-mutation patterns observed in chronic HBV infection patients.</p> <p>Methods</p> <p>Total 192 blood samples of chronic HBV infection patients were included. Direct PCR sequencing on the target region of HBV genome was successfully conducted in 157 samples. The rest 35 samples were analyzed by clone sequencing. Only the nucleotide substitutions with their frequencies no less than 10% were included in multi-mutation analysis with the exception for the polymorphic sites between genotypes B and C.</p> <p>Results</p> <p>Five high frequency mutations (≥10%) were found in BCP and preC region. Thirteen types of multi-mutations in one fragment were observed, among which 3 types were common combinations (≥5%). The top three multi-mutations were A1762T/G1764A (36%), A1762T/G1764A/G1896A (11%) and T1753(A/C)/A1762T/G1764A/G1896A (8%). Patients with multi-mutations in viral genomes (≥3) were more likely to have liver cirrhosis or hepatocellular carcinoma (OR = 3.1, 95% CI: 1.6-6.0, P = 0.001). G1896A mutation seemed to be involved in liver disease progression independent of the patient age (OR = 3.6, 95% CI: 1.5-8.6; P = 0.004). In addition, patients with more viral mutations detected (≥3) were more likely to be HBeAg negative (OR = 2.7, 95% CI: 1.1-6.4; P = 0.027). Moreover, G1776A mutation was shown to contribute to HBeAg negativity in our study (OR = 8.6, 95% CI: 1.2-44.9; P = 0.01).</p> <p>Conclusions</p> <p>Patients with advanced liver diseases and with HBeAg negativity more likely have multi-mutations in HBV genomes but with different mutation combination patterns. G1896A mutation appears to be independent of infection history.</p> |
| first_indexed | 2024-12-11T12:05:55Z |
| format | Article |
| id | doaj.art-30c084cc42514d228e9f5bc62d259c02 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-11T12:05:55Z |
| publishDate | 2010-09-01 |
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| series | BMC Infectious Diseases |
| spelling | doaj.art-30c084cc42514d228e9f5bc62d259c022022-12-22T01:07:56ZengBMCBMC Infectious Diseases1471-23342010-09-0110127110.1186/1471-2334-10-271Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progressionZhang DakeMa SufangZhang XinZhao HanqingDing HuiguoZeng Changqing<p>Abstract</p> <p>Background</p> <p>Mutations in the basic core promoter (BCP) and its adjacent precore (preC) region in HBV genome are common in chronic hepatitis B patients. However, the patterns of mutation combinations in these two regions during chronic infection are less understood. This study focused on single base mutations in BCP and preC region and the multi-mutation patterns observed in chronic HBV infection patients.</p> <p>Methods</p> <p>Total 192 blood samples of chronic HBV infection patients were included. Direct PCR sequencing on the target region of HBV genome was successfully conducted in 157 samples. The rest 35 samples were analyzed by clone sequencing. Only the nucleotide substitutions with their frequencies no less than 10% were included in multi-mutation analysis with the exception for the polymorphic sites between genotypes B and C.</p> <p>Results</p> <p>Five high frequency mutations (≥10%) were found in BCP and preC region. Thirteen types of multi-mutations in one fragment were observed, among which 3 types were common combinations (≥5%). The top three multi-mutations were A1762T/G1764A (36%), A1762T/G1764A/G1896A (11%) and T1753(A/C)/A1762T/G1764A/G1896A (8%). Patients with multi-mutations in viral genomes (≥3) were more likely to have liver cirrhosis or hepatocellular carcinoma (OR = 3.1, 95% CI: 1.6-6.0, P = 0.001). G1896A mutation seemed to be involved in liver disease progression independent of the patient age (OR = 3.6, 95% CI: 1.5-8.6; P = 0.004). In addition, patients with more viral mutations detected (≥3) were more likely to be HBeAg negative (OR = 2.7, 95% CI: 1.1-6.4; P = 0.027). Moreover, G1776A mutation was shown to contribute to HBeAg negativity in our study (OR = 8.6, 95% CI: 1.2-44.9; P = 0.01).</p> <p>Conclusions</p> <p>Patients with advanced liver diseases and with HBeAg negativity more likely have multi-mutations in HBV genomes but with different mutation combination patterns. G1896A mutation appears to be independent of infection history.</p>http://www.biomedcentral.com/1471-2334/10/271 |
| spellingShingle | Zhang Dake Ma Sufang Zhang Xin Zhao Hanqing Ding Huiguo Zeng Changqing Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression BMC Infectious Diseases |
| title | Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression |
| title_full | Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression |
| title_fullStr | Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression |
| title_full_unstemmed | Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression |
| title_short | Prevalent HBV point mutations and mutation combinations at BCP/preC region and their association with liver disease progression |
| title_sort | prevalent hbv point mutations and mutation combinations at bcp prec region and their association with liver disease progression |
| url | http://www.biomedcentral.com/1471-2334/10/271 |
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