Genetic Mutations of the Hepatitis B Virus Genome S and BCP/Pre-C Regions of the Hepatitis B Virus (HBV) Genome in Chronic HBV Infection in Fujian Province of China

LI Dong 1 YANG Xiuhui 1,2 CHEN Zhifei 1 ZHANG Suhan 1 ZHENG Ningxuan 1 PAN Weiyi 1,2 ZHOU Yong 1,2 ZHENG Kuicheng 1,2

(1.Key Laboratory of Zoonosis Research of Fujian Province, Fujian Center for Disease Control & Prevention , Fuzhou, China 350001)
(2.Teaching Base of Public Health School of Fujian Medical University , Fuzhou, China 350001)
【Novelty】Based on the previous study selected the sequence of HBV gene S area, basic core promoter (BCP) and the Pre- C mutation as a key discussion,More than previous articles is one of the gene function research.This paper discuss three functional areas, and found that these mutations may cause virus antigen expression, vaccine escape, patients condition change, etc., so should strengthen the monitoring in patients with these mutations.

【Abstract】To investigate the molecular characteristics of the hepatitis B virus (HBV) genome in chronic HBV-infected patients in Fujian Province of China, serum samples were collected from patients with chronic HBV infection. HBV DNA was extracted for amplification of surface genes, basic core promoter (BCP) genes and precore (Pre-C) genes amplification. Polymerase chain reaction (PCR) products were sequenced and compared with standard sequences in GenBank. Sequencher, MEGA5 and Bioedit were used for mutation analyses of the HBV genome. We obtained 82 complete sequences of HBV. In all sequences, 56 were B genotype and 26 were C genotype. Gene sequencing revealed that these HBV gene sequences in S (23.2%), BCP (61.0%) and Pre-C (29.3%) regions had a different degree of variation. The frequency of a determinant amino acid (aa) variant was 45. 8%. Those mutation sites might be correlated with severe liver diseases and immune escape, such as the sites of aa126, aa129 and aa145. Analyses revealed that site G1896A (19.5%), G1764A (11.0%) and A1762T (9.8%) remained the major mutations in the BCP/Pre-C region. Simultaneously, the high mutation rate of A1752G (25.6%) in BCP merited attention. G1764A (χ2 = 6.498, P = 0.013), A1896G (10.444, 0.001) and A1762T/G1764A) mutations were more likely to occur in HBeAg–negative samples. A1846T (χ2 = 11.882, P = 0.003), A1762T (6.561, 0.038) and A1896G (6.958, 0.030) mutations had some relevances with HBV DNA load. In conclusion, people with chronic HBV infection in Fujian Province of China had different degrees of variation in HBV gene-function areas. Some of these mutations were associated with HBeAg expression, HBV DNA load, immune evasion of vaccines, and occurrence of hepatocellular carcinoma. Patients with these mutations need strengthened monitoring.

【Keywords】 Hepatitis B virus (HBV) ; Genetic mutations; Basic core promoter (BCP) ; Pre-C region;

【DOI】

【Funds】 National Science and Technology Major Project of China (No. 2012ZX10002001-002-002) National Science and Technology Major Project of China (No. 2017ZX10103008-004)

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This Article

ISSN:1000-8721

CN: 11-1865/R

Vol 34, No. 04, Pages 491-497

June 2018

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Abstract

  • Materials and methods
  • Results
  • Discussion
  • References