Background
The treatment outcomes of Hepatitis C virus (HCV) with direct-acting antivirals (DAAs) may be affected by host immunogenetic factors. While IL28B gene polymorphisms are known to impact therapy response, the influence of FOXP3 promoter polymorphisms remains unclear. This study aims to assess the correlation between IL28B and FOXP3 gene variants and the treatment outcomes of Sofosbuvir/Daclatasvir (SOF/DAC) in HCV-infected Egyptian patients.
Methods
This retrospective cohort study included 99 HCV patients who achieved a sustained virological response at week 12 (SVR12), defined as undetectable HCV RNA throughout the 12-week post-treatment follow-up period, and 63 patients who did not achieve SVR12. L28B 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 in representative samples from both groups.
Results
IL28B rs12979860 T˃C and FOXP3 rs2232365 A˃G polymorphisms significantly increased the risk of non-response. Responder patients had elevated IL28B serum levels, while FOXP3 levels were decreased as 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 SOF/DAC response in HCV patients.
CONCLUSION: These findings could provide insights into the responsiveness of DAAs in HCV treatment, leading to personalized medicine and better therapeutic decision-making.
References
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- Nahon P, Cobat A. Human genetics of HCV infection phenotypes in the era of direct-acting antivirals. Hum Genet. 2020;139(6–7):855–63. 10.1007/s00439-020-02136-4.
- Oda JMM, Hirata BKB, Guembarovski RL, Watanabe MAE. Genetic polymorphism in FOXP3 gene: Imbalance in regulatory T-cell role and development of human diseases. J Genet. 2013;92(1):163–71.
