Nucleotide divergences in the core promoter and precore region of genotype D hepatitis B virus in patients with persistently elevated or normal ALT levels

• Published in: Journal of clinical virology Vol. 21; no. 1; pp. 91 - 101
• Main Authors: Bozdayı, A.Mithat, Bozkaya, Hakan, Repat Türkyılmaz, Ahmet, Sarýodlu, Mustafa, Çetinkaya, Hülya, Karayalçın, Selim, Yurdaydın, Cihan, Uzunalimoğlu, Özden
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.04.2001; Elsevier Science
• Subjects: Adolescent; Adult; Aged; Alanine aminotransferase; Alanine Transaminase - blood; Base Sequence; Biological and medical sciences; Child; Codon, Terminator; Core promoter; DNA, Viral - blood; DNA, Viral - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Variation; Genotype; HBV; Hemoglobin E; Hepatitis Antibodies - blood; Hepatitis B e Antigens - blood; Hepatitis B e Antigens - immunology; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - pathology; Hepatitis B, Chronic - virology; Humans; Male; Microbiology; Middle Aged; Molecular Sequence Data; Mutation; Nucleotide divergence; Precore; Promoter Regions, Genetic; Viral Core Proteins - genetics; Alanine aminotransferase; Precore; Core promoter; Mutation; HBV; Nucleotide divergence; Human; Transcription promoter; Viremia; Orthohepadnavirus; Hepatic disease; Infection; Virus; Viral hepatitis B; Chronic; Codon; Hepadnaviridae; Viral disease; Digestive diseases; Serum; Hepatitis B virus
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/S1386-6532(01)00148-2

Background: Mutation in the hepatitis B virus precore codon 28, creating a translational stop codon and double 1762–1764 T/A mutations in the core promoter region, controlling the transcription of the precore RNA and the core RNA have been suggested to correlate with the HBeAg status of patients with HBV infection. Objectives: The aim of the study was to further investigate the association of nucleotide divergences in both core promoter and precore regions with liver cell injury (reflected by ALT levels) in patients with chronic HBV infection. Study Design: The sequences of the core promoter and the precore region of HBV isolated from 67 patients, all having genotype D and subtype ayw were analyzed . The patients were divided into two groups and four subgroups according to their HBeAg and Anti-HBe status, and ALT profile. Results: It was found that the nucleotide divergences in the core promoter but not in the precore region were higher in patients having persistently elevated serum ALT than in serum ALT normal patients in both HBeAg positive and Anti-HBe positive groups ( P<0.05). The number of T/A and A1896 stop codon mutations did not yield a statistically significant difference between ALT normal and elevated groups. It was also found that 1762–1764 T/A and precore A 1896 mutation existed in five and six out of 29 HBeAg positive patients, respectively. In 38 anti-HBe positive patients, 1762–1764 T/A and precore A1896 mutation were detected in three and 16 patients respectively, and coexisted in 10 patients. Conclusions: Precore A 1896 stop codon mutation seems to play an essential role in the loss of HBeAg in Turkish patients. Serum viremia levels of HBV in patients having precore stop codon and/or T/A mutation were not significantly different from the other patients carrying wild type strains. Nucleotide variability in the core promoter region may be one of the factors linked to hepatitis B disease activity.