PDF(Pubmed)
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.
摘要：
引入直接作用的抗病毒治疗后，埃及HCV感染的患病率有所下降。然而,治疗反应受各种因素影响，特别是宿主免疫遗传学，如IL-28B和FOXP3多态性。当前的研究检查了FOXP3基因启动子区域中SNP对HCV感染的埃及患者的影响，以及IL28B基因中的SNP。这项研究涉及99名HCV患者，他们在12周的DAA治疗后达到SVR12，而63名HCV患者经历了治疗失败。使用实时PCR鉴定IL28Brs12979860SNP，而IL28Brs8099917，FOXP3rs3761548和rs222365SNP使用RFLP-PCR进行分析。使用ELISA技术对来自两组的代表性样品中的IL28B和FOXP3的血清水平进行定量。IL28Brs12979860T>C(P=0.013)和FOXP3rs222365A>G多态性(P=0.008)显著增加无应答的风险。与非反应者相比，反应者的IL28B血清水平更高（P=0.046），FOXP3水平更低（P<0.001）。回归分析显示IL28Brs12979860和FOXP3rs222365与治疗反应之间存在关联，独立于年龄和性别。开发了一种预测模型，其敏感性为76.2％，特异性为91.9％，用于评估HCV患者的DAAs反应。我们的发现证实IL28Brs12979860T>C和FOXP3rs222365A>G多态性显著影响HCV埃及患者的DAA治疗反应。IL-28B水平较低以及FOXP3水平较高与反应不良有关。我们的结果可能会导致对DAA反应性的新见解，有助于个性化医疗和改善HCV患者的治疗决策。
