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However, treatment response is influenced by various factors, particularly host immunogenetics such as <jats:italic>IL-28B<\/jats:italic> and FOXP3 polymorphisms. The current study examined the impact of SNPs in the <jats:italic>FOXP3<\/jats:italic> gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved\u00a099 HCV patients who achieved SVR12 after a 12\u00a0week DAA\u00a0treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, <jats:italic>FOXP3<\/jats:italic> rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and <jats:italic>FOXP3<\/jats:italic> were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T\u2009&gt;\u2009C (<jats:italic>P<\/jats:italic>\u2009=\u20090.013) and <jats:italic>FOXP3<\/jats:italic> rs2232365 A\u2009&gt;\u2009G polymorphisms (<jats:italic>P<\/jats:italic>\u2009=\u20090.008) were found to significantly increase the risk of non-response. Responders had higher <jats:italic>IL28B<\/jats:italic> serum levels (<jats:italic>P<\/jats:italic>\u2009=\u20090.046) and lower <jats:italic>FOXP3<\/jats:italic> levels (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and <jats:italic>FOXP3<\/jats:italic> 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\u2009&gt;\u2009C and FOXP3 rs2232365 A\u2009&gt;\u2009G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of <jats:italic>IL-28B<\/jats:italic> 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s10238-024-01432-x","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T16:02:07Z","timestamp":1723132927000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C"],"prefix":"10.1007","volume":"24","author":[{"given":"Aya Ismail","family":"Abdelaziz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eman","family":"Abdelsameea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Abdel-Samiee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar E.","family":"Ghanem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara A.","family":"Wahdan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa A.","family":"Elsherbiny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeinab","family":"Zakaria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-8280","authenticated-orcid":false,"given":"Samar S.","family":"Azab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"1432_CR1","unstructured":"World Health Organization: WHO [Internet]. 2023 [cited 2023 Aug 28]. 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