Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 8;24(1):184.
doi: 10.1007/s10238-024-01432-x.

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

Aya Ismail Abdelaziz  1 , Eman Abdelsameea  2 , Mohamed Abdel-Samiee  2 , Samar E Ghanem  3 , Sara A Wahdan  4 , Doaa A Elsherbiny  4 , Zeinab Zakaria  1 , Samar S Azab  5
Affiliations

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

Aya Ismail Abdelaziz et al. Clin Exp Med. .

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.

Keywords: DAA; Daclatasvir; FOXP3; HCV; IL28B; Sofosbuvir.

PubMed Disclaimer

Conflict of interest statement

The authors have read the journal’s policy on disclosure of potential conflicts of interest, and they all wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

All authors have read the journal’s authorship statement and agree to it. By your journal’s policy, we confirm that the material contained in the manuscript is original and has not been published and is not being submitted elsewhere. The authors qualify for authorship and have no financial or personal relationships that might lead to a conflict of interest. This manuscript is being submitted online in accordance with your policies for this type of submission.

The Authors hereby grant the Journal full and exclusive rights to the manuscript, all revisions, and the full copyright. The Journal rights include but are not limited to the following: (1) to reproduce, publish, sell, and distribute copies of the manuscript, selections of the manuscript, and translations and other derivative works based upon the manuscript, in print, audio-visual, electronic, or by any media now or hereafter known or devised; (2) to license reprints of the manuscript to third persons for educational photocopying; (3) to license others to create abstracts of the manuscript and to index the manuscript; (4) to license secondary publishers to reproduce the manuscript in print, microform, or any computer-readable form, including electronic on-line databases; and (5) to license the manuscript for document delivery. These exclusive rights run the full term of the copyright, and all renewals and extensions thereof.

Figures

Fig. 1
Fig. 1
Amplification plots of the genotypes for Interleukin IL28B (rs12979860) polymorphism. The amplification curves are based on the fluorescence intensity variation (ΔRn) according to the number of PCR cycles for the wild-type Heterozygous CT (A), Homozygous CC (B), and Mutant-Type Homozygous TT (C). RFLP of the amplified product of (D) For the genotyping IL28B rs8099917, the 552 bp PCR product was digested by BsrDI enzyme. The T allele is not cut by the enzyme where the G allele yields 322 and 230 bp products. (E) For the genotyping FOXP3 rs3761548, the 487 bp product was digested with PstI enzyme. The C allele is not cut by the enzyme, whereas the A allele yields 329 and 158 bp products (F) For the genotyping FOXP3 rs2232365, the 374 bp PCR product was digested with BsMBI enzyme. The A allele is not cut by the enzyme, whereas the G allele yields 188 and 186 bp products
Fig. 2
Fig. 2
Linkage disequilibrium between genotyped SNPs. The number in each square represents the pairwise LD relationship (r2) between the IL28B (rs12979860, rs8099917) and FOXP3 (rs2232365, rs3761548) SNPs in Egyptian HCV patients treated with Daclatasvir (DAC) 60 mg/day and Sofosbuvir (SOF) 400 mg/day and varying red color represent the linkage disequilibrium values for that pair as measured by D′ (bright red shows high D′). The numbers in the gray-shaded area represent inferred listed in Table 3. The inferred in each haplotype block and the linkage between blocks are shown. The lines between haplotype blocks indicate the linkage frequency with a thick line for > 10% and a thin line for a frequency from 1–10%. Haplotype frequency within each haplotype block is shown next to each haplotype
Fig. 3
Fig. 3
Comparison of (A) the serum level of IL28B between responder and non-responder subject; (B) IL28B (rs12979860) genotypes against average serum IL28B concentration; (C) the serum level of FOXP3 between responder and non-responder subjects and FOXP3 rs2232365 (D) and rs3761548 (E) genotypes against average serum FOXP3 concentration (F) Boxplot for the serum level of ALT among C and T Alleles of responders and non-responders a, b: Statistically Significant of AA and AG genotypes of FOXP3 rs2232365 in non-responder compared to GG genotype in responders using Kruskal-Wallis test followed by Dunn’s test for multiple comparison. c, d: Statistically Significant of AA and AC genotypes of FOXP3 rs3761548 in non-responder compared to AC genotype in responders using Kruskal-Wallis test followed by Dunn’s test for multiple comparison. e: Statistically Significant of TT genotype of IL28B rs12979860 in non-responder compared to TT genotype in responders using Kruskal-Wallis test followed by Dunn’s test for multiple comparison *Statistically Significant between C allele in responder and T allele in non-responder using Kruskal-Wallis test followed by Dunn’s test for multiple comparison
Fig. 4
Fig. 4
Receiving operating curve (ROC) of the multivariate analysis for DAA treatment response in chronic HCV Egyptian patients treated with Daclatasvir (DAC) 60 mg/day and Sofosbuvir (SOF) 400 mg/day. Area under the curve (AUC) was 0.917 (95% CI = 0.871- 0.963). It is represented a sensitivity of 76.2%, specificity of 91.9%, and total accuracy of 85.8%
See this image and copyright information in PMC

References

    1. World Health Organization: WHO [Internet]. 2023 [cited 2023 Aug 28]. Hepatitis C. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
    1. Manns MP, Maasoumy B, Rice CM. Breakthroughs in hepatitis C research: from discovery to cure. Nat Rev Gastroenterol Hepatol. 2022;19:533–50. - PMC - PubMed
    1. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. 2000;355(9207):887–91. - PubMed
    1. Esmat G, El-Sayed MH, Hassany M, Doss W, Waked I. One step closer to elimination of hepatitis C in Egypt. Vol. 3, The Lancet Gastroenterology and Hepatology. Elsevier Ltd; 2018. p. 665. - PubMed
    1. Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol. 2013;10(9):553–62. - PubMed

LinkOut - more resources