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Article: A genetic variant of CXCR4 predicts pegylated interferon-alpha treatment response in HBeAg-positive chronic hepatitis B patients

TitleA genetic variant of CXCR4 predicts pegylated interferon-alpha treatment response in HBeAg-positive chronic hepatitis B patients
Authors
Keywordschemokine receptor 4 (CXCR4)
chronic hepatitis B (CHB)
hepatitis B virus (HBV)
pegylated interferon-alpha (PegIFNα)
single-nucleotide polymorphism (SNP)
Issue Date14-Feb-2024
PublisherAmerican Society for Microbiology
Citation
Journal of Clinical Microbiology, 2024, v. 62, n. 2 How to Cite?
Abstract

Chemokine receptor 4 (CXCR4) plays a vital role in immunoregulation during hepatitis B virus (HBV) infection. This study aimed to screen single-nucleotide polymorphisms (SNPs) of CXCR4 for predicting pegylated interferon-alpha (PegIFNα) therapy response in chronic hepatitis B (CHB) patients. This retrospective cohort study enrolled a total of 945 CHB patients in two cohorts (Cohort 1, n = 238; Cohort 2, n = 707), and all the patients were hepatitis B e antigen (HBeAg)-positive and treated with PegIFNα for 48 weeks and followed up for 24 weeks. Twenty-two tag SNPs were selected in CXCR4 and its flanking region. A polygenic score (PGS) was utilized to evaluate the cumulative effect of multiple SNPs. The relationships between CXCR4 SNPs and PGS and PegIFNα treatment response were explored in the two cohorts. Among the 22 candidate SNPs of CXCR4, rs28367495 (T > C) was significantly linked to PegIFNα treatment response in both cohorts. In patients with more number of rs28367495 C allele, a higher rate of combined response (CR, defined as HBeAg seroconversion and HBV DNA level < 3.3 log10 IU/mL; P = 1.51 × 10−4), a lower mean hepatitis B surface antigen (HBsAg) level (P = 4.76 × 10−4), and a higher mean HBsAg decline (P = 3.88 × 10−4) at Week 72 were achieved. Moreover, a PGS integrating CXCR4_rs28367495 and five previously reported SNPs was strongly correlated with CR (P = 1.26 × 10−13), HBsAg level (P = 4.90 × 10−4), and HBsAg decline (P = 0.005) in all the patients of the two cohorts. CXCR4_rs28367495 is a promising indicator for predicting the responsiveness to PegIFNα treatment for HBeAg-positive CHB patients. The new PGS may further improve the prediction performance.


Persistent Identifierhttp://hdl.handle.net/10722/340225
ISSN
2023 Impact Factor: 6.1
2023 SCImago Journal Rankings: 1.653
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLuo, M-
dc.contributor.authorDong, C-
dc.contributor.authorLiang, X-
dc.contributor.authorNa, R-
dc.contributor.authorZhou, B-
dc.contributor.authorHou, J-
dc.contributor.authorJiang, D-K-
dc.date.accessioned2024-03-11T10:42:36Z-
dc.date.available2024-03-11T10:42:36Z-
dc.date.issued2024-02-14-
dc.identifier.citationJournal of Clinical Microbiology, 2024, v. 62, n. 2-
dc.identifier.issn0095-1137-
dc.identifier.urihttp://hdl.handle.net/10722/340225-
dc.description.abstract<p>Chemokine receptor 4 (CXCR4) plays a vital role in immunoregulation during hepatitis B virus (HBV) infection. This study aimed to screen single-nucleotide polymorphisms (SNPs) of <em>CXCR4</em> for predicting pegylated interferon-alpha (PegIFNα) therapy response in chronic hepatitis B (CHB) patients. This retrospective cohort study enrolled a total of 945 CHB patients in two cohorts (Cohort 1, <em>n</em> = 238; Cohort 2, <em>n</em> = 707), and all the patients were hepatitis B e antigen (HBeAg)-positive and treated with PegIFNα for 48 weeks and followed up for 24 weeks. Twenty-two tag SNPs were selected in <em>CXCR4</em> and its flanking region. A polygenic score (PGS) was utilized to evaluate the cumulative effect of multiple SNPs. The relationships between <em>CXCR4</em> SNPs and PGS and PegIFNα treatment response were explored in the two cohorts. Among the 22 candidate SNPs of <em>CXCR4</em>, rs28367495 (T > C) was significantly linked to PegIFNα treatment response in both cohorts. In patients with more number of rs28367495 C allele, a higher rate of combined response (CR, defined as HBeAg seroconversion and HBV DNA level < 3.3 log<sub>10</sub> IU/mL; <em>P</em> = 1.51 × 10<sup>−4</sup>), a lower mean hepatitis B surface antigen (HBsAg) level (<em>P</em> = 4.76 × 10<sup>−4</sup>), and a higher mean HBsAg decline (<em>P</em> = 3.88 × 10<sup>−4</sup>) at Week 72 were achieved. Moreover, a PGS integrating <em>CXCR4</em>_rs28367495 and five previously reported SNPs was strongly correlated with CR (<em>P</em> = 1.26 × 10<sup>−13</sup>), HBsAg level (<em>P</em> = 4.90 × 10<sup>−4</sup>), and HBsAg decline (<em>P</em> = 0.005) in all the patients of the two cohorts. <em>CXCR4</em>_rs28367495 is a promising indicator for predicting the responsiveness to PegIFNα treatment for HBeAg-positive CHB patients. The new PGS may further improve the prediction performance.</p>-
dc.languageeng-
dc.publisherAmerican Society for Microbiology-
dc.relation.ispartofJournal of Clinical Microbiology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectchemokine receptor 4 (CXCR4)-
dc.subjectchronic hepatitis B (CHB)-
dc.subjecthepatitis B virus (HBV)-
dc.subjectpegylated interferon-alpha (PegIFNα)-
dc.subjectsingle-nucleotide polymorphism (SNP)-
dc.titleA genetic variant of CXCR4 predicts pegylated interferon-alpha treatment response in HBeAg-positive chronic hepatitis B patients-
dc.typeArticle-
dc.identifier.doi10.1128/jcm.01396-23-
dc.identifier.scopuseid_2-s2.0-85185195419-
dc.identifier.volume62-
dc.identifier.issue2-
dc.identifier.eissn1098-660X-
dc.identifier.isiWOS:001169655200004-
dc.identifier.issnl0095-1137-

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