Single-nucleotide polymorphism of Toll-like receptor 4 and interleukin-10 in response to interferon-based therapy in Egyptian chronic hepatitis C patients

Abstract

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world. It has been suggested that not only the virus but also the interaction between the virus and the host immune system is important in determining the course of the infection and the response to interferon (IFN)-based therapy. While the adaptive immune system plays a critical role in HCV infection, the innate immune system has only been recognized recently. Toll-like receptors (TLRs) form the cornerstone of the innate immune response. Interleukin-10 (IL-10) is one of the upstream regulators of TLR4. A possible interplay between TLR4 and IL-10 has been suggested. The present study aimed to investigate the role of single-nucleotide polymorphisms (SNPs) in TLR4 and IL-10-1082 and the expression levels of these proteins in predicting the response to treatment in chronic HCV patients. A total of 83 chronic HCV-infected Egyptian patients treated with peg-IFN-a2b-ribavirin combination therapy and 40 healthy subjects were included in this study. SNPs in the TLR4 rs2149356 and IL-10-1082 genes and their serum levels were assessed. Within the responders group, T/T and A/A genotypes were the significantly most frequent genotypes of TLR4 and IL-10-1082, respectively. Moreover, a higher frequency of T/T and A/A was found to be associated with lower serum TLR4 and IL-10 levels in our responder patients. In addition, subjects with the T/T genotype in the healthy control group had a lower serum TLR4 level than those with other genotypes. We conclude that the SNPs

Toll-like receptors activation, signaling, and targeting: an overview

“…It was demonstrated that the genetic polymorphisms of TLR2 and TLR4 were not associated with asthma and allergic rhinitis, but significant association was found between these genetic variants and the disease severity in children (Hussein et al, 2012). It was revealed that TLR2 and TLR4 polymorphisms have no influence in HCV among Egyptian children (Soliman et al, 2014), while TLR4 polymorphism may be important predictor for HCV therapy in adults (Sadik et al, 2015). There was no significant association between TLR4 polymorphism and colorectal cancer (CRC), but higher serum level of it was associated with a diagnostic prospect in CRC patients (Bassuny, 2017).…”

“…However, sustained or excessive immune system activation is deleterious and leads to irreversible changes in organ structure and function (Wang et al, 2015). Toll-like receptors (TLRs) is a family of pattern recognition receptors (PRRs) that form the cornerstone of the innate immune response (Sadik et al, 2015). Toll was originally discovered as a gene controlling the dorsal-ventral polarity of the Drosophila embryo, but was later found to be involved in anti-fungal immunity (Anderson et al, 1985).…”

The associations between Toll-like receptor 4 gene polymorphisms and hepatitis C virus infection: a systematic review and meta-analysis

“…The TLR4 rs2149356 T allele reduces the risk of HHC compared with HCV patients and healthy controls [22]. Moreover, TT genotype frequency increased in responder patients versus non-responders to peg-IFN-α2b-ribavirin [23]. In our study, we assessed different questions from previous reports.…”

“…Thereafter, 134 articles were removed based on those containing unrelated titles, abstracts and full text, resulting in 7 eligible articles. Accordingly, only seven eligible articles were enrolled in this study for quality assessment and meta-analysis ( Figure 1) [17][18][19][20]22,23,34]. Subsequently, quality assessment was performed via NOS and included studies were shown to be of high and moderate quality (Supplemental Table 1).…”

“…Previous evidence has suggested that rs2149356 significantly reduced the risk of HCC and delayed interferon therapy. However, this position lacks association evidence which is related to HCV infection [22,23].…”