Association of Toll-like receptor 3 and Toll-like receptor 9 single-nucleotide polymorphisms with hepatitis C virus persistence among Egyptians.

Toll-like receptors (TLRs) give the innate immune system a considerable specificity for a large range of pathogens. TLR3 detects dsRNA of viruses while TLR9 recognizes bacterial and viral unmethylated CpG motifs. This study examined whether there is a potential association between single-nucleotide polymorphisms (SNPs) in the TLR3.rs3775290 (c.1377C/T), TLR9.rs5743836 (-1237T→C) and TLR9.rs352140 (G2848A) genes and HCV infection among Egyptian patients and healthcare workers (HCWs). We enrolled 546 subjects (409 HCWs and 137 patients) divided into four groups: group 1 included 265 seronegative, aviremic subjects; group 2 included 25 seronegative, viremic subjects; group 3 included 87 subjects with spontaneously resolved HCV infection; and group 4 included 169 chronic HCV patients. All subjects were genotyped for TLR3.rs3775290, TLR9.rs5743836 and TLR9.rs352140 SNPs by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. TLR3.rs3775290 "CC" genotype was associated with chronic HCV infection, where there was a significantly greater frequency of this genotype among chronic patients when compared to subjects with spontaneously resolved infection (63.9% vs. 51.9%; p = 0.033; OR = 1.639 and 95% CI = 0.94-2.84). However, this SNP did not correlate with the HCV RNA load among the chronic subjects (p > 0.05). There was no significant difference in TLR9.rs5743836 and TLR9.rs352140 genotype distribution between groups (p > 0.05). Lack of association between the three SNPs was found, as the three SNPs are located on two different chromosomes. In conclusion, the TLR3.rs3775290 "CC" genotype was associated with HCV chronicity, while the TLR9 gene may not play a major role in HCV infection.

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

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.