CXCR7 genetic variant predicts treatment response of pegylated-interferon α in HBeAg-positive chronic hepatitis B patients

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Mengqi Luo , Xinghe Liang , Bin Zhou , Jinlin Hou , De-Ke Jiang
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Abstract

Objectives

CXC chemokine receptor 7 (CXCR7) plays pivotal roles in different virus infections. However, no research focused on the role of CXCR7 in hepatitis B virus (HBV)-infected patients. The primary aim of this study is to elucidate the role of CXCR7 in predicting the treatment response of chronic hepatitis B (CHB) patients undergoing pegylated interferon-alpha (PegIFNα) therapy.

Methods

Two cohorts with a total of 945 Chinese CHB patients (Cohort 1, n = 238; Cohort 2, n = 707) were enrolled in this retrospective study, all the patients were positive for hepatitis B e antigen (HBeAg) and received PegIFNα treatment for 48 weeks and followed-up for 24 weeks post-treatment. Nineteen tag single-nucleotide polymorphisms (SNPs) were selected within and surrounding the CXCR7 gene region. The associations of CXCR7 SNPs and polygenic score (PGS) with PegIFNα treatment response were investigated in the two cohorts.

Results

Among the 19 candidate SNPs of CXCR7, rs2952665 (A > G) was significantly associated with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <3.3log10IU/mL, P = 0.002) and hepatitis B surface antigen (HBsAg) decline (P = 0.015) in the two cohorts at week 72. Furthermore, a PGS comprising CXCR7_rs2952665 and five additional SNPs, which were previously recognized as biomarkers of PegIFNα treatment response, demonstrated a robust correlation with both CR (P = 1.38 × 10−12) and HBsAg decline (P = 0.003) in all the patients.

Conclusion

This research illustrated that CXCR7_rs2952665 is a promising predictor of the PegIFNα therapy efficiency in Chinese HBeAg-positive CHB patients. A PGS consisting of CXCR7_rs2952665 and five previously reported SNPs predicts treatment response to PegIFNα better.

CXCR7 基因变异可预测 HBeAg 阳性慢性乙型肝炎患者对聚乙二醇干扰素 α 的治疗反应
目的CXC趋化因子受体 7(CXCR7)在不同的病毒感染中发挥着关键作用。然而,还没有研究关注 CXCR7 在乙型肝炎病毒(HBV)感染患者中的作用。本研究的主要目的是阐明 CXCR7 在预测接受聚乙二醇干扰素-α(PegIFNα)治疗的慢性乙型肝炎(CHB)患者的治疗反应中的作用。所有患者均为乙型肝炎e抗原(HBeAg)阳性,接受PegIFNα治疗48周,治疗后随访24周。研究人员在 CXCR7 基因区及其周围选择了 19 个标记单核苷酸多态性(SNPs)。在两个队列中调查了 CXCR7 SNPs 和多基因评分(PGS)与 PegIFNα 治疗反应的关系。结果在 CXCR7 的 19 个候选 SNPs 中,rs2952665 (A > G) 与两个队列在第 72 周时的合并应答(CR,定义为 HBeAg 血清转换和 HBV DNA 水平 <3.3log10IU/mL,P = 0.002)和乙肝表面抗原(HBsAg)下降(P = 0.015)显著相关。此外,由 CXCR7_rs2952665 和另外五个 SNPs 组成的 PGS 与所有患者的 CR(P = 1.38 × 10-12)和 HBsAg 下降(P = 0.003)都有很强的相关性。由 CXCR7_rs2952665 和之前报道的五个 SNPs 组成的 PGS 能更好地预测 PegIFNα 的治疗反应。
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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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