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Interleukin 28A.rs12980602 and interleukin 28B.rs8103142 genotypes could be protective against HCV infection among Egyptians

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Abstract

Previous studies showed that interleukin (IL)-28B gene polymorphisms were associated with hepatitis C Virus (HCV) infection and treatment outcomes. We tested whether single-nucleotide polymorphisms (SNPs) in IL-28A and IL-28B are associated with HCV infection among Egyptians with HCV genotype 4 infections. We enrolled 144 chronic HCV patients, 72 spontaneously resolved HCV subjects, and 69 healthy controls. Four SNPs in IL-28A and IL-28B genes (IL-28A.rs12980602, IL-28B.rs12979860, IL-28B.rs8099917, and IL-28B.rs8103142) were genotyped. The most frequent IL-28B haplotype “TCT” was significantly more frequent in HCV-infected subjects than in HCV negative subjects (62.2% vs. 48.6%, respectively; p = 0.005). The frequency of IL-28A.rs12980602 “T” allele was significantly higher than the “C” allele in healthy controls compared to HCV-infected subjects (p < 0.001) with the “TT” genotype significantly higher in healthy controls compared to HCV-infected subjects (p < 0.001) with no association with viral load (p = 0.11) among chronically infected subjects. The results, also, confirmed the previous role of IL-28B SNPs in predicting HCV infection outcome. Importantly, IL-28B.rs8099917 “TT” genotype was significantly associated with low viral load in HCV-infected subjects, while the remaining three SNPs did not. The three IL-28B SNPs were in linkage disequilibrium (D′ > 0.68; r2 > 0.43) for all comparisons in HCV patients, while there was no linkage disequilibrium of IL-28A polymorphisms and the three IL-28B SNPs. In conclusion, IL-28A.rs12980602 and IL-28B.rs8103142 TT genotype could be protective against HCV infection. Also, IL-28B.rs12979860, IL-28B.rs8099917, and IL-28B.rs8103142 SNPs predicted the outcome of HCV infection among genotype-4-infected Egyptians. Moreover, IL-28B.rs8099917 SNP affected the viral load in chronic HCV patients.

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Acknowledgments

We would like to thank Dr. Nabiel Mikhail and Enas S. Aziz (Egyblood) for their technical help with the data. We thank Mrs. Hoayda M. Ahmed and Dr. Mohamed Abdel-Samee (from the NLI) for their assistance with sample collection and enrollment of the subjects. We particularly appreciate Dr. Gehan Galal (Director of Egyblood R&D Department), Dr. Nelly Sedky, and Dr. Hala Hussein (previous Egyblood CEOs,) for their support throughout the conduct of the study.

Funding

This study was supported by the European Union 6th Framework Program contract no. 0374435 to the HEPACIVAC consortium and by the European Union 7th Framework Program contract no. 260844 to the HEPACUTE consortium.

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Authors and Affiliations

  1. The Holding Company for Biological Products and Vaccines (VACSERA), 51 Wizaret El-Zeraa St., Agouza, Giza, 22311, Egypt

    Zainab A. Zakaria, Mohamed Hashem & Sayed Abdelwahab

  2. Biomedical Research Laboratory, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt

    Zainab A. Zakaria

  3. Department of Hepatology and Gastroenterology, Imperial College, St. Mary’s Hospital, London, W21NY, UK

    Susanne Knapp & Mark Thursz

  4. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD21201, USA

    Mohamed Hashem

  5. Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia, 32511, Egypt

    Hassan Zaghla & Imam Waked

  6. Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, 61511, Egypt

    Sayed Abdelwahab

  7. Department of Microbiology, College of Pharmacy, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia

    Sayed Abdelwahab

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  1. Zainab A. Zakaria
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Zakaria, Z.A., Knapp, S., Hashem, M. et al. Interleukin 28A.rs12980602 and interleukin 28B.rs8103142 genotypes could be protective against HCV infection among Egyptians. Immunol Res 67, 123–133 (2019). https://doi.org/10.1007/s12026-018-9035-2

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