الفهرس 
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Abstract
Hepatitis C has been considered as a serious health concern and a main cause of chronic liver disease, with around 200 million infected people worldwide. It is often asymptomatic, but once established, it can progress to hepatic cirrhosis, hepatic failure or hepatocellular carcinoma.
Concerning genes that can influence susceptibility to hepatitis caused by HCV, Toll-like receptors (TLRs) represent plausible candidates. TLRs are a family of transmembrane proteins that are expressed in most immune cells and are main components of innate immune system and they play an essential role in detection of components derived from a wide range of pathogens. However, imbalanced host immune response thorough TLR-dependent signaling pathways may cause inflammatory and autoimmune diseases. TLR7 (located on chromosome X) is particularly implicated in several infectious and autoimmune diseases.
The aim of this study was to investigate the expression level of TLR7 in peripheral blood of patients with resolving and non-resolving HCV infections and patients with HCC, comparing it with normal individuals, and to determine the association between TLR7 (rs179009 gene) polymorphism and chronic hepatitis C infection with and without hepatocellular carcinoma.
Ninety eight Egyptian participants were enrolled in the study; 30 chronic HCV patients (16 males & 14 females), 30 spontaneously resolved patients (18 males & 12 females), 20 HCC patients (16 males & 4 females) and 18 age- and sex-matched healthy controls (4 males & 14 females).
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The TLR7 polymorphism analyzed was SNP rs179009 (A/G). The analysis was performed by Taq-Man allelic discrimination using Taq-Man SNP genotyping assay and real-time PCR. Similarly, TLR7 expression level was evaluated using real-time PCR according to the Manufacturer’s protocols (Thermo Scientific, EU/Lithuania).
Our results revealed that TLR7 expression was significantly lower in HCV carriers and HCC patients compared to patients who naturally cleared their infection and healthy controls (P=0.015). Regarding TLR7 polymorphism, the data were analyzed in males and females separately. In females, the AA genotype and the A allele were significantly predominant in HCV clearance group (83.33%), healthy controls (78.6%) and HCC patients (75%), compared to the persistently HCV-infected females (21.4%) (P<0.05). On the other hand, the AG and GG genotypes were over represented in chronic HCV-infected females than healthy controls and spontaneously resolved patients. In males, no significant differences were detected between the studied groups in the allele frequencies of the TLR7 rs179009 polymorphism. The A genotype was nearly equally represented in the different patient groups (87.5% in HCV carriers, 93.8% in HCC patients, 94.4% in HCV clearance) and controls (100%). The G genotype was not detected in male healthy controls and no significant difference was observed in its distribution among the patient groups (P>0.05).
TLR7 SNP rs179009 association was studied in relation to the HCV outcome. It was found that the carriage of the AA genotype and the A allele was significantly associated with HCV clearance in females. The AA genotype was significantly higher in females who cleared their HCV infection as compared to HCV carriers (83.33% vs.
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21.4%). But, both the AG genotype (OR=0.03, 95% CI=0.003-0.381) and the G allele (P<0.05, OR=0.16, 95% CI=0.04-0.68) were significantly higher among chronic HCV-infected females (64.3% and 46.4%) when compared with females who cleared their HCV infection (8.33% and 12.5%). On the other hand, the A or the G genotypes couldn‟t predict HCV outcome significantly among males (OR=0.41, 95% CI =0.03-5.03, P=0.591).
The TLR7 genotype frequencies in the HCV-infected patients (groups A and B) compared to the healthy controls revealed that there was no significant association between the TLR7 SNP genotypes with the outcome of HCV infection among the male or female subjects (P>0.05). Moreover, the study revealed that no significant association was observed between the TLR7 SNP genotypes with HCC susceptibility among healthy individuals whether in male or female subjects (P>0.05). Furthermore, by comparing the distribution of TLR7 SNP genotypes among HCV-infected patients (groups A and B) with the HCC cases, no significant association was detected between the TLR7 genotypes and the risk of HCC susceptibility among HCV-infected subjects whether in male or female patients (P>0.05).