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Interleukin 28A.rs12980602 and interleukin 28B.rs8103142 genotypes could be protective against HCV infection among Egyptians
Authors:Zakaria  Zainab A.  Knapp  Susanne  Hashem  Mohamed  Zaghla  Hassan  Thursz  Mark  Waked  Imam  Abdelwahab  Sayed
Affiliation:1.The Holding Company for Biological Products and Vaccines (VACSERA), 51 Wizaret El-Zeraa St., Agouza, Giza, 22311, Egypt
;2.Biomedical Research Laboratory, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
;3.Department of Hepatology and Gastroenterology, Imperial College, St. Mary’s Hospital, London, W21NY, UK
;4.Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD21201, USA
;5.Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia, 32511, Egypt
;6.Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, 61511, Egypt
;7.Department of Microbiology, College of Pharmacy, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia
;
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.

Keywords:
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