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

Abstract

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.

Role of resistin, IL-6 and NH2-terminal portion proBNP in the pathogenesis of cardiac disease in type 2 diabetes mellitus

“…The high serum level of IL-6 had a predictive function in the pathogenesis of insulin resistance and cardiac complications in patients with diabetes. [26][27][28][29][30][31] Also, Cheng et al 32 found that increased plasma concentrations of resistin were strongly associated with subsequent development of heart failure. The association of resistin with heart failure persisted after adjustment for established heart failure risk factors, obesity, markers of insulin resistance and inflammation, and concentrations of NT-proBNP, and after exclusion of prevalent and incident CHD.…”

Association of the polymorphism of the Toll-like receptor (TLR)-3 and TLR-9 genes with hepatitis C virus-specific cell-mediated immunity outcomes among Egyptian health-care workers

“…We previously demonstrated that the TLR-3.rs3775290 'CC' genotype was associated with HCV chronicity, and that the TLR-9 gene played no major role in this infection [14]. This study identified the role of TLR-3.rs3775290 (c.1377C/T), TLR-9.rs5743836 (−1237T→C) and TLR-9.…”

Pattern Recognition Receptors: Significance of Expression in the Liver

“…Mosaad et al ( 2019 ) showed that the heterozygous CT genotype of TLR3rs 3775290 appeared to be a susceptibility risk factor of chronic HCV infection, while the homozygous CC and of TLR7rs 179008, TLR9rs 352140 single nucleotide polymorphism (SNPs), including the combined genotype (CC-AT-GA) were protective. Earlier, another group of authors (Hamdy et al 2018 ) found that the TLR3rs 3775290, “CC” genotype was associated with chronic HCV infection, this SNP, however, did not correlate with the HCV RNA load of the chronic subjects. These studies indicate the potential value of genetic exploration of TLRs in this disease, in spite of evident discrepancies between individual reports.…”