Association Of Estrogen And Estrogen Receptor αPolymorphisms With The Outcome Of HCV Infection Among High Risk Population

Section1Study on associations of plasma estradiol level with HCV infection and liver function in paid blood donors[Background] Form1980s to1990s, some illegal and commercial blood centers were founded in Zhenjiang City. These nonstandard behaviors of blood donation led to the spread of hepatitis C virus and other blood transmission diseases to blood donors. Most of these people sold their blood with the method of plasmapheresis from1989to1993, and also some people had the history of whole blood donation. Most of them were housewives and resided in the town for a long time. Meanwhile they had never receipt any HCV detection and antiviral treatment.[Objectives] To explore the associations of plasma estradiol (E2) level with HCV infection and liver function in paid blood donors, and to provide evidence for the pathogenesis and prevention measures of HCV infection.[Methods] The study population were consisted of195subjects (59males and136females over50-year old) who were paid blood donors from a certain city in Jiangsu province around1990. All subjects were categorized into three groups, including95persistent HCV carriers,44HCV natural clearance subjects, and56healthy controls. The subjects’plasma E2concentration and liver function characteristics (including alanine aminotransferase [ALT], aspartate aminotransferase[AST], total bilirubin [Tbil], direct bilirubin [Dbil], gamma-glutamyl transpeptidase [GGT] and alkaline phosphatase [ALP]) were performed. Covariance analysis, partial correlation and multivariate logistic regression were used to discover the associations of plasma E2level with outcomes of HCV infection and liver function.[Results] Controlling for the number of whole blood and/or plasma donation and liver disease (fatty liver and/or cirrhosis), the ALT (P=0.003) and AST (P=0.025) levels showed statistically significant differences among the3groups. In addition, a partial correlation analysis indicated that the level of E2was weakly negatively correlated with ALT, AST, GGT and ALP. However, the correlation did not show statistically significance (all P>0.05). The multivariate logistic regression implicated that age was independently associated with normal ALT values in chronic HCV infection (OR=1.122,95%CI=1.036-1.215).[Conclusion] The administration of blood donation should be enhanced. Large, well-designed follow-up studies with ethnically-diverse populations are warranted to further elucidate the impact of E2on HCV infection outcomes and liver function condition. Section2Association of Genetic variants in estrogen receptor a with HCV infection susceptibility and viral clearance in a high-risk Chinese population[Background] Currently, about180million people had ever infected hepatitis C virus all over the world. China is considered a relatively high endemic area of HCV infection, with an estimated prevalence rate of3.2%in the general population. Different individuals get different prognosis after infecting HCV. It not only related to the type of virus strain but also related to some gene polymorphism of the host. The polymorphism of some gene is maybe associated to the immunologic function of host and lead to different outcome of HCV infection.[Objectives] To test the hypothesis that genetic variants of estrogen receptor a (ERa) are associated with the outcomes of hepatitis C virus (HCV) infection.[Methods] We genotyped the seven single nucleotide polymorphisms (SNPs)(rs2077647, rs9340799, rs2234693, rs1801132, rs9322354, rs2228480and rs3798577) of ERa and conducted a case-control study in a high-risk Chinese population, including429HCV spontaneous clearance cases,880persistent infection cases and1,174uninfected controls.[Results] The C allele of rs2234693was significantly associated with increased susceptibility to HCV infection [dominant model:adjusted odds ratio (OR)=1.377,95%confidence interval (CI)=1.126-1.778], and the risk effect remained significant among the younger (≤55years) and hemodialysis subjects (all P<0.007). The other three SNPs variant genotypes also showed significant correlation with elevated risk of HCV infection in different strata (rs2077647:in males; rs9340799:in blood donors; rs1801132:in younger subjects, all P<0.007). It was also discovered that carriage of rs2228480A allele was more prone to develop persistent HCV infection (dominant model:adjusted OR=1.203,95%CI=1.154-1.552), and the risk effect was more evident in females and blood donors (all P<0.007). Haplotype analyses (rs2077647, rs9340799and rs2234693) showed that, compared with the most frequent haplotype TAT, CAC played a risk effect in subgroups of younger (P=3.24×10-3) and male (P=5.51×10-4), whereas CAT expressed a protective effect in females (P=2.27×10-4) for HCV infection susceptibility.[Conclusion] We first report that these SNPs (rs2077647, rs9340799, rs2234693, rs1801132and rs2228480) in ERa can influence the outcomes of HCV infection in a high-risk Chinese population.