Association of Toll-like receptor (TLR) 3 & 9 genes’ polymorphism with
Hepatitis C virus-specific cell-mediated immunity outcome among Egyptian
healthcare workers
Abstract
Immune response variations could define successful resistance to
Hepatitis C Virus (HCV) infection. Toll-like receptors (TLR)-3 are
innate detectors of dsRNA viruses while bacterial and viral unmethylated
CpG motifs are recognized by TLR9. We previously reported that
TLR3.rs3775290 “CC” genotype was associated with HCV chronicity, while
TLR9 gene played no major role in this infection. This study identified
the role of TLR3.rs3775290 (c.1377C/T), TLR9.rs5743836 (-1237T→C) and
TLR9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of
HCV-specific cell-mediated immunity (CMI) among Egyptian healthcare
workers (HCWs) and patients. We enrolled 546 subjects (409 HCWs and 137
patients) divided into four groups. Group1: 265 seronegative, aviraemic
subjects; group2: 25 seronegative, viraemic subjects; group3: 87
subjects with spontaneously resolved HCV infection; and group4: 169
chronic HCV HCWs and patients. All subjects were genotyped by
PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the
TLR3.rs3775290, TLR9.rs5743836 and TLR9.rs352140 SNPs. We, also,
quantified HCV-specific CMI in 265 HCWs distributed among the four
groups using an interferon gamma (IFN-γ) enzyme-linked immunospot
(ELISpot) assay in response to nine HCV genotype 4a overlapping 15mer
peptide pools covering the whole viral genome. No statistically
significant difference was found between CMI responding subjects with
different HCV states and TLR3.rs3775290 genotype or TLR9.rs352140.
However, there was a significant relationship between the outcome of the
HCV-specific CMI and the TLR9.rs5743836 genotype among the responding
subjects (p=0.005) and the chronic HCV patients (p=0.044). In
conclusion, TLR9.rs5743836 SNP; but not TLR3.rs3775290 or TLR9.rs352140
genotypes; could predict the outcome of HCV-specific CMI responses among
genotype-4-infected Egyptians.