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A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population
BACKGROUND: CD40 is an important immune costimulatory molecule that has recently been found to be associated with chronic hepatitis B. This study aims to explore the association between CD40 polymorphisms and HBV infection, as well as to investigate the impact of different rs1883832 genotypes on CD4...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697618/ http://dx.doi.org/10.1097/HC9.0000000000000331 |
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author | Wu, Wennan Xu, Siyi Zeng, Yongbin Yu, Luoli Chen, Tianbin Shang, Hongyan Liu, Can Yang, Bin Ou, Qishui |
author_facet | Wu, Wennan Xu, Siyi Zeng, Yongbin Yu, Luoli Chen, Tianbin Shang, Hongyan Liu, Can Yang, Bin Ou, Qishui |
author_sort | Wu, Wennan |
collection | PubMed |
description | BACKGROUND: CD40 is an important immune costimulatory molecule that has recently been found to be associated with chronic hepatitis B. This study aims to explore the association between CD40 polymorphisms and HBV infection, as well as to investigate the impact of different rs1883832 genotypes on CD40 expression and its effect on the progression of chronic HBV infection. METHODS: We genotyped rs1883832 in 3433 individuals using MassARRAY, and quantified the CD40 expression, including CD40 mRNA, sCD40, and mCD40. The CD40 and HBV infection indicators were assessed to investigate the potential function of rs1883832 in suppressing HBV replication in HepG2.2.15 and HepAD38, CD40L in cytotoxic t lymphocytes (CTLs) and interferon-γ, TNF-α, granzyme B, and perforin were measured to elucidate the mechanism by which CD40 inhibits HBV replication. RESULTS: Our study revealed that the frequencies of CC genotype and C allele of rs1883832 were significantly higher in immune recovery compared to chronic hepatitis B. Individuals with CC genotype exhibited significantly elevated CD40 in serum and B cells compared to TT genotypes in chronic hepatitis B. Additionally, CD40 is capable of inhibiting HBV replication and transcription in hepatocytes by means of interaction with CD40L. A significant negative correlation was found between HBV DNA, HBeAg, and mCD40. Conversely, the expressions of ALT and mCD40 showed a positive correlation, which aligns with the trend of CD40L. CONCLUSIONS: rs1883832 C allele may have a protective role in HBV immune recovery. This protective effect could potentially be attributed to the regulation of CD40 expression. The activation of the anti-HBV immune response, which occurs through binding CD40L on CTL, can suppress HBV DNA replication and potentially facilitate immune recovery in HBV infection. |
format | Online Article Text |
id | pubmed-10697618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-106976182023-12-06 A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population Wu, Wennan Xu, Siyi Zeng, Yongbin Yu, Luoli Chen, Tianbin Shang, Hongyan Liu, Can Yang, Bin Ou, Qishui Hepatol Commun Original Article BACKGROUND: CD40 is an important immune costimulatory molecule that has recently been found to be associated with chronic hepatitis B. This study aims to explore the association between CD40 polymorphisms and HBV infection, as well as to investigate the impact of different rs1883832 genotypes on CD40 expression and its effect on the progression of chronic HBV infection. METHODS: We genotyped rs1883832 in 3433 individuals using MassARRAY, and quantified the CD40 expression, including CD40 mRNA, sCD40, and mCD40. The CD40 and HBV infection indicators were assessed to investigate the potential function of rs1883832 in suppressing HBV replication in HepG2.2.15 and HepAD38, CD40L in cytotoxic t lymphocytes (CTLs) and interferon-γ, TNF-α, granzyme B, and perforin were measured to elucidate the mechanism by which CD40 inhibits HBV replication. RESULTS: Our study revealed that the frequencies of CC genotype and C allele of rs1883832 were significantly higher in immune recovery compared to chronic hepatitis B. Individuals with CC genotype exhibited significantly elevated CD40 in serum and B cells compared to TT genotypes in chronic hepatitis B. Additionally, CD40 is capable of inhibiting HBV replication and transcription in hepatocytes by means of interaction with CD40L. A significant negative correlation was found between HBV DNA, HBeAg, and mCD40. Conversely, the expressions of ALT and mCD40 showed a positive correlation, which aligns with the trend of CD40L. CONCLUSIONS: rs1883832 C allele may have a protective role in HBV immune recovery. This protective effect could potentially be attributed to the regulation of CD40 expression. The activation of the anti-HBV immune response, which occurs through binding CD40L on CTL, can suppress HBV DNA replication and potentially facilitate immune recovery in HBV infection. Lippincott Williams & Wilkins 2023-12-01 /pmc/articles/PMC10697618/ http://dx.doi.org/10.1097/HC9.0000000000000331 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Original Article Wu, Wennan Xu, Siyi Zeng, Yongbin Yu, Luoli Chen, Tianbin Shang, Hongyan Liu, Can Yang, Bin Ou, Qishui A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population |
title | A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population |
title_full | A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population |
title_fullStr | A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population |
title_full_unstemmed | A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population |
title_short | A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population |
title_sort | genetic variant in the cd40 gene is related to hbv infection in the chinese han population |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697618/ http://dx.doi.org/10.1097/HC9.0000000000000331 |
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