PMID- 28694662 OWN - NLM STAT- MEDLINE DCOM- 20180713 LR - 20181113 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 23 IP - 23 DP - 2017 Jun 21 TI - Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-naive Korean patients infected with genotype C2. PG - 4222-4232 LID - 10.3748/wjg.v23.i23.4222 [doi] AB - AIM: To report naturally occurring mutations in the reverse transcriptase region (RT) of hepatitis B virus (HBV) polymerase from treatment naive Korean chronic patients infected with genotype C2. METHODS: Here, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment naive Korean patients chronically infected with hepatitis B genotype C2. The patients had two distinct clinical statuses: 59 patients with chronic hepatitis (CH) and 72 patients with hepatocellular carcinoma (HCC). The deduced amino acids (AAs) at 42 previously reported potential nucleos(t)ide analog resistance (NAr) mutation positions in the RT region were analyzed. RESULTS: Potential NAr mutations involving 24 positions were found in 79 of the 131 patients (60.3%). Notably, AA substitutions at 2 positions (rt184 and rt204) involved in primary drug resistance and at 2 positions (rt80 and rt180) that functioned as secondary/compensatory mutations were detected in 10 patients (1 CH patient and 9 HCC patients) and 7 patients (1 CH and 6 HCC patients), respectively. The overall mutation frequencies in the HCC patients (3.17%, 96/3024 mutations) were significantly higher than the frequencies in the CH patients (2.09%, 52/2478 mutations) (P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and rt204 were found to be significantly related to HCC from treatment naive Korean patients. CONCLUSION: Our data showed that naturally occurring NAr mutations in South Korea might contribute to liver disease progression (particularly HCC generation) in chronic patients with genotype C2 infections. FAU - Kim, Ji-Eun AU - Kim JE AD - Ji-Eun Kim, So-Young Lee, Hong Kim, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. FAU - Lee, So-Young AU - Lee SY AD - Ji-Eun Kim, So-Young Lee, Hong Kim, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. FAU - Kim, Hong AU - Kim H AD - Ji-Eun Kim, So-Young Lee, Hong Kim, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. FAU - Kim, Ki-Jeong AU - Kim KJ AD - Ji-Eun Kim, So-Young Lee, Hong Kim, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. FAU - Choe, Won-Hyeok AU - Choe WH AD - Ji-Eun Kim, So-Young Lee, Hong Kim, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. FAU - Kim, Bum-Joon AU - Kim BJ AD - Ji-Eun Kim, So-Young Lee, Hong Kim, Bum-Joon Kim, Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Antiviral Agents) RN - 0 (DNA, Viral) RN - EC 2.7.7.49 (RNA-Directed DNA Polymerase) SB - IM MH - Adult MH - Aged MH - Antiviral Agents/therapeutic use MH - Carcinoma, Hepatocellular/virology MH - DNA Mutational Analysis MH - DNA, Viral/genetics MH - Disease Progression MH - Drug Resistance, Neoplasm MH - Drug Resistance, Viral/genetics MH - Female MH - *Genotype MH - Hepatitis B virus/*enzymology/genetics MH - Hepatitis B, Chronic/virology MH - Humans MH - Liver Neoplasms/virology MH - Male MH - Middle Aged MH - *Mutation MH - Polymerase Chain Reaction MH - RNA-Directed DNA Polymerase/*genetics MH - Republic of Korea PMC - PMC5483496 OTO - NOTNLM OT - Chronic hepatitis OT - Hepatitis B virus OT - Hepatocellular carcinoma OT - Polymerase OT - Potential nucleos(t)ide analog resistance OT - Reverse transcriptase COIS- Conflict-of-interest statement: There was no conflict of interest exists. EDAT- 2017/07/12 06:00 MHDA- 2018/07/14 06:00 PMCR- 2017/06/21 CRDT- 2017/07/12 06:00 PHST- 2017/01/13 00:00 [received] PHST- 2017/03/28 00:00 [revised] PHST- 2017/05/09 00:00 [accepted] PHST- 2017/07/12 06:00 [entrez] PHST- 2017/07/12 06:00 [pubmed] PHST- 2018/07/14 06:00 [medline] PHST- 2017/06/21 00:00 [pmc-release] AID - 10.3748/wjg.v23.i23.4222 [doi] PST - ppublish SO - World J Gastroenterol. 2017 Jun 21;23(23):4222-4232. doi: 10.3748/wjg.v23.i23.4222.