Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C.

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Experimental Medicine Pub Date : 2024-08-08 DOI:10.1007/s10238-024-01432-x
Aya Ismail Abdelaziz, Eman Abdelsameea, Mohamed Abdel-Samiee, Samar E Ghanem, Sara A Wahdan, Doaa A Elsherbiny, Zeinab Zakaria, Samar S Azab
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Abstract

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients.

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免疫遗传学多态性和表达对慢性丙型肝炎直接作用抗病毒药物反应的影响
埃及在引入直接作用抗病毒疗法后,HCV 感染率有所下降。然而,治疗反应受多种因素影响,尤其是宿主免疫遗传学,如 IL-28B 和 FOXP3 多态性。本研究考察了 FOXP3 基因启动子区 SNPs 和 IL28B 基因 SNPs 对感染 HCV 的埃及患者的影响。本研究涉及 99 例 HCV 患者,他们在接受 12 周 DAA 治疗后获得了 SVR12,而 63 例 HCV 患者治疗失败。通过实时 PCR 鉴定了 IL28B rs12979860 SNP,通过 RFLP-PCR 分析了 IL28B rs8099917、FOXP3 rs3761548 和 rs2232365 SNP。采用 ELISA 技术对两组代表性样本的血清 IL28B 和 FOXP3 水平进行了定量分析。结果发现,IL28B rs12979860 T > C(P = 0.013)和 FOXP3 rs2232365 A > G(P = 0.008)多态性显著增加了无应答的风险。应答者血清中 IL28B 水平较高(P = 0.046),FOXP3 水平较低(P C 和 FOXP3 rs2232365 A > G 多态性明显影响 HCV 埃及患者的 DAA 治疗应答。较低水平的 IL-28B 和较高水平的 FOXP3 与不良反应有关。我们的研究结果可能会使人们对 DAA 反应性有新的认识,从而有助于个性化医疗和改善 HCV 患者的治疗决策。
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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