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循环趋化因子水平和受体多态性有潜力作为慢性丙型肝炎感染患者纤维化分期的生物标志物。

Circulating chemokine levels and receptor polymorphisms have potential as biomarkers for fibrosis stages in patients with chronic hepatitis C infection.

作者信息

Teneke Seren Oğultekin, Serin Mehmet Sami, Öksüz Zehra, Temel Gülhan Orekici, Yaraş Serkan, Üçbilek Enver, Sezgin Orhan

机构信息

Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Mersin University, Mersin, Turkey.

Faculty of Medicine, Department of Biostatistics, Mersin University, Mersin, Turkey.

出版信息

Mol Biol Rep. 2025 Jan 18;52(1):138. doi: 10.1007/s11033-025-10244-5.

DOI:10.1007/s11033-025-10244-5
PMID:39825971
Abstract

BACKGROUND

Chemokines and their receptors, which regulate lymphoid organ development and immune cell trafficking, are integral to the mechanisms underlying viral control, hepatic inflammation, and liver damage in chronic hepatitis C (CHC) infection. This study explores the potential relationship between serum chemokine levels/polymorphisms and hepatitis C infection in affected individuals, with a particular focus on their utility as biomarkers across different stages of fibrosis.

METHODS AND RESULTS

Serum levels of the chemokines CXCL11, CXCL12, and CXCL16 were measured in patients with mild/moderate and advanced fibrosis due to CHC, as well as in healthy controls, using the ELISA method. The CXCL12 rs1801157 and CXCL16 rs2277680 polymorphisms were analyzed in blood samples from patients and healthy controls through RT-qPCR. Serum levels of CXCL11, CXCL12, and CXCL16 were significantly elevated in patients with advanced fibrosis compared to healthy controls. Furthermore, CXCL11 levels were markedly higher in patients with advanced fibrosis than in those with mild/moderate fibrosis. The frequency of the CXCL12 rs1801157 AA genotype was significantly higher in the advanced fibrosis group compared to the healthy control group. Similarly, the CXCL16 rs2277680 GA genotype was significantly more prevalent in the advanced fibrosis group than in the mild/moderate fibrosis group.

CONCLUSIONS

The current study highlights that, in addition to the potential association between chemokine levels/polymorphisms and an increased risk of disease complications and pathological progression in CHC infection, serum CXCL11 levels and the CXCL16 rs2277680 allel polymorphism may be important factors in determining the fibrosis stage of hepatitis C infection.

摘要

背景

趋化因子及其受体调节淋巴器官发育和免疫细胞运输,是慢性丙型肝炎(CHC)感染中病毒控制、肝脏炎症及肝损伤机制的重要组成部分。本研究探讨血清趋化因子水平/多态性与受影响个体丙型肝炎感染之间的潜在关系,尤其关注其作为不同纤维化阶段生物标志物的效用。

方法与结果

采用ELISA法检测CHC所致轻度/中度和重度纤维化患者以及健康对照者血清趋化因子CXCL11、CXCL12和CXCL16的水平。通过RT-qPCR分析患者和健康对照者血样中CXCL12 rs1801157和CXCL16 rs2277680多态性。与健康对照者相比,重度纤维化患者血清CXCL11、CXCL12和CXCL16水平显著升高。此外,重度纤维化患者的CXCL11水平明显高于轻度/中度纤维化患者。与健康对照组相比,重度纤维化组CXCL12 rs1801157 AA基因型频率显著更高。同样,CXCL16 rs2277680 GA基因型在重度纤维化组比轻度/中度纤维化组更普遍。

结论

本研究强调,除了趋化因子水平/多态性与CHC感染中疾病并发症风险增加及病理进展之间的潜在关联外,血清CXCL11水平和CXCL16 rs2277680等位基因多态性可能是决定丙型肝炎感染纤维化阶段的重要因素。

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一种新算法显示出在慢性丙型肝炎中区分肝纤维化阶段的卓越能力。
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Study of CXCL9-11 gene polymorphisms in liver fibrosis among patients with chronic hepatitis C.慢性丙型肝炎患者肝纤维化中 CXCL9-11 基因多态性的研究。
Pathog Dis. 2021 Mar 20;79(3). doi: 10.1093/femspd/ftab007.
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Circulating levels of CXCL11 and CXCL12 are biomarkers of cirrhosis in patients with chronic hepatitis C infection.循环 CXCL11 和 CXCL12 水平是慢性丙型肝炎感染患者肝硬化的生物标志物。
Cytokine. 2019 May;117:72-78. doi: 10.1016/j.cyto.2019.02.006. Epub 2019 Feb 28.
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EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version).欧洲超声医学与生物学联合会肝脏超声弹性成像临床应用指南及建议,2017年更新版(长篇)
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Serum CXCL10, CXCL11, CXCL12, and CXCL14 chemokine patterns in patients with acute liver injury.血清 CXCL10、CXCL11、CXCL12 和 CXCL14 趋化因子谱在急性肝损伤患者中的变化。
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Future Oncol. 2018 Jun;14(13):1261-1271. doi: 10.2217/fon-2017-0613. Epub 2018 May 9.
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