Single Nucleotide Polymorphisms Of Toll-like Receptor 7in Hepatitis C Virus Infection Patients From A High-risk Chinese Population

Section 1A study on correlation of plasma IL-18 level with HCV infection and viral genotyping in paid blood donors[Background] The nonstandard behaviors of blood donation would lead to the wide spread of blood transmission diseases among those blood donors, such as hepatitis C.The methods they applied were plasmapheresis and whole blood donation. Most of them had never receipt HCV detection or antiviral treatment.[Objectives] To study the relationship between plasma IL-18 level and the HCV infection outcomes, HCV genotyping, and liver function characteristic among paid blood donors, and to explore the role of plasma IL-18 level in HCV susceptibility and the disease progression.[Methods] The study population included 150 subjects who were collected from a certain city in Jiangsu province during April to July 2012. The participants were divided into three groups according to the result of anti-HCV and HCV RNA detection, i.e., 50 healthy controls, 50 spontaneous clearance and 50 persistent infection subjects. The concentration of plasma IL-18 and liver function characteristics was measured. We also applied the covariance analysis and partial correlation to figure the associations of plasma IL-18 level with HCV infection outcomes, liver function and HCV genotypes.[Results] The number of whole blood donation and plasma donation, ALT, AST, GGT,TP and IL-18 levels were different among the three groups and the differences were of statistical significant(all P<0.05). The plasma IL-18 level, ALT and AST levels and the number of whole blood donation and plasma donation showed statistically significant differences among 3 groups(all P<0.05) after controlling for the age, sex,the number of whole blood donation and liver disease(fatty liver and/or cirrhosis).Moreover, the difference of the plasma IL-18 concentration among patients with different HCV genotyping(1b, non-1b, and mixed type) was statistically significant(H=8.64, P=0.013). The partial correlation analysis indicated that the plasma IL-18 level was significantly positively correlated with ALT and AST level(r1=0.279,P=0.022;r2=0.302,P=0.013).[Conclusion] Plasma IL-18 level may play a role in the development and pathogenesis of HCV infection. It is not only involved in HCV clearance but also damage the liver cells. Different plasma IL-18 levels among individuals with different HCV genotypes could partly explain the disparity of HCV infection outcomes. To further elucidate the impact of IL-18 on HCV infection and the liver function condition, more well-designed studies with lager and ethnically-diverse populations are warranted.Section 2Single Nucleotide Polymorphis msof Toll- Like Receptor 7in Hepatitis C Virus Infection Patients fro ma High-Risk Chinese Populatio n[Background] Currently, near 180 million people are infected with hepatitis C virus(HCV) and over 3.5 million new sufferers occurring annually around the world. With an estimated prevalence rate of 3.2%, China is considered as a relatively high endemic area. After infected with HCV, different people would get different prognosis.The virus genotype as well as the genetic polymorphisms of some gene of the host were account for this. The polymorphisms of genes associated with the host immunity could lead to different outcomes of disease.[Objectives] To investigate the associations of three single nucleotide polymorphisms(SNPs) of Toll like receptor 7(TLR7), rs179016, rs5743733, and rs1634323, with the susceptibility to HCV infection and clearance.[Methods] Three single nucleotide polymorphisms(SNPs)(rs179016, rs5743733,and rs1634323) of TLR7 were genotyped in 444 HCV spontaneous clearance subjects,732 persistent infection subjects, and 1107 healthy controls.[Results] The G allele of rs1634323 was related to the protection from persistent infection among females(dominant model: odds ratio(OR)=0.558, 95 % confidence interval(CI)=0.348–0.894, P=0.015). This protective effect was more evident in blood donation and HCV non-1 genotype-infected subgroups(all P<0.05). The carriage of rs179016 C allele was more prone to develop persistent infection(OR=1.444, 95 % CI=1.096–1.903, P=0.009) in males, and the risk effect remained significant among older(>50 years), hemodialysis(HD), and HCV-1 and HCV non-1genotypes-infected subjects(all P<0.05). Haplotype analyses showed that CCA haplotype among females was correlated with the elevated risk of HCV susceptibility while the carriage of GGA was more prone to be infected with HCV and CCA was more likely to develop persistent infection(all P<0.05) among males.[Conclusion] Our results first demonstrated that the carriage of rs179016 C allele had a negative effect on spontaneous clearance of HCV among males while rs1634323 G allele conferred a protective effect against persistent infection among female subjects.