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Published on: November 7, 2018
[Mutation of hepatitis B virus S gene in children with hepatitis B virus-associated glomerulonephritis]
Hui Zhu1, Hong-zhu Lu, Jian-hua Zhou
1Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Insights
Mutations in the Hepatitis B virus (HBV) S gene were identified in most children with HBV-associated glomerulonephritis (HBV-GN). These genetic changes, particularly those affecting phosphorylation sites, may contribute to the development of HBV-GN.
Area of Science:
- Virology
- Nephrology
- Genetics
Context:
- Hepatitis B virus-associated glomerulonephritis (HBV-GN) is an immune complex-mediated kidney disease.
- Understanding the genetic basis of HBV-GN is crucial for developing targeted therapies.
Purpose:
- This study aimed to identify mutations in the Hepatitis B virus (HBV) S gene in children diagnosed with HBV-GN.
- The research also investigated the impact of these mutations on protein structure and potential pathogenic mechanisms.
Summary:
- Serum HBV DNA from 53 children (30 with HBV-GN, 5 with HBV-carrying nephrosis, 18 HBV carriers) was analyzed for HBV S gene mutations using PCR and sequencing.
- Seventy percent of HBV-GN patients exhibited single nucleotide changes in the HBV S gene, with 76.2% resulting in amino acid substitutions.
- Most amino acid substitutions involved threonine, serine, and tyrosine, which are potential phosphorylation sites, suggesting a role in HBV-GN pathogenesis.
Impact:
- Identifies specific HBV S gene mutations associated with glomerulonephritis in children.
- Highlights the potential role of altered HBV protein phosphorylation in the pathogenesis of HBV-GN.
- Provides insights for future research into diagnostic markers and therapeutic strategies for HBV-GN.
Objective:
Hepatitis B virus-associated glomerulonephritis (HBV-GN) is an immune complex-mediated glomerulonephritis. The present study was conducted to identify HBV S gene mutation in children with HBV-GN.
Methods:
Serum HBV DNA was extracted in 53 children, including 30 with HBV-GN, 5 with HBV-carrying nephrosis (control group 1), and 18 HBV carriers (control group 2). HBV S gene sequence was amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly and compared with AY167097.1, an epidemic HBV strain in China.
Results:
(1) The adw serotype of HBV was found in all the 30 cases with HBV-GN, 5 cases with HBV-carrying nephrosis and 17 HBV carriers except for 1, in whom adr serotype was identified. (2) HBV genotype B was found in 29 children with HBV-GN, 5 cases with HBV-carrying nephrosis and 17 HBV carriers, genotype E was found in a child with HBV-GN, and genotype C in an HBV carrier. (3) A total of 17 kinds of different single nucleotide change in HBV S gene were identified in 21 of 30 (70%) HBV-GN patients. Among them, 16 of 21 (76.2%) nucleotide mutations resulted in amino acid substitution. It was interesting that most (11/16, 68.8%) amino acid substitutions involved threonine, serine and tyrosine, the potential phosphorylation sites of mitogen-activated protein kinase (MAPK) and protein tyrosine kinase (PTK) in HBV protein. Single nucleotide changes which didn not result in amino acid substitution were found in 2 HBV-carrying nephrosis patients, 2 HBV carriers and 5 cases with HBV-GN.
Conclusion:
Single nucleotide changes in HBV S gene were found in most children with HBV-GN. Most mutations in HBsAg resulted in amino acid substitutions involving threonine, serine and tyrosine, which may play a role in the pathogenesis of HBV-GN.
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