1. Functional polymorphisms of TLR8 are associated with hepatitis C virus infection.
- Author
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Wang, Chiou‐Huey, Eng, Hock‐Liew, Lin, Kuei‐Hsiang, Liu, Hsiang‐Chun, Chang, Cheng‐Hsien, and Lin, Tsun‐Mei
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GENETIC polymorphisms ,TOLL-like receptors ,PUBLIC health ,RNA viruses ,HEPATITIS C virus ,MESSENGER RNA ,NF-kappa B ,PATIENTS - Abstract
Chronic hepatitis C virus (HCV) infection is a worldwide threat to public health. Toll-like receptor 8 (TLR8) is critical for eliminating RNA viruses, and variation within the TLR8 gene may alter the function of TLR8 in response to HCV infection. Our previous study demonstrated that the TLR8-129G>C (rs3764879) and TLR8+1G>A (rs3764880) variants were in complete linkage disequilibrium, and that the frequency of TLR8-129C/+1A was significantly higher in male patients with HCV infection compared with the healthy controls. In the present study, we found that the promoter activity of TLR8-129G was higher than that of TLR8-129C in THP-1 cells. Moreover, TLR8-129G mRNA stability and competitive DNA-binding ability were significantly lower than that of TLR8-129C. To investigate the functional effects of TLR8 polymorphisms, we compared the nuclear factor- κB (NF- κB)-driven luciferase activity in HEK293 cells transfected with the TLR8 variants. TLR8+1A plasmids induced less NF- κB signalling than did those transfected with TLR8+1G after 20 μ m CL075 ( P = 0·011) stimulation. We also analysed the mRNA expression and cytokine production in whole blood and monocytes from people of various genotypes stimulated ex vivo by the interferon- γ and TLR7/8 agonist CL075, R848. TLR8 expression in CD14
+ cells derived from volunteers with TLR8-129G/+1G was significantly higher than that derived from TLR8-129C /+1A, and interleukin-12p40 production was higher in volunteers with TLR8-129G/+1G after stimulation. The data indicate that variations in TLR8 genes may modulate immune responses during HCV infection. [ABSTRACT FROM AUTHOR]- Published
- 2014
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