Association Of 25-hydroxyvitamin D And Vitamin D Binding Protein Gene Polymorphisms With The Outcomes Of HCV Infection In A High-risk Chinese Han Population

Section 1Study on associations of plasma 25-hydroxyvitamin D concentration with HCV inf'ection and liver function[Background]Hepatitis C virus infection is one of the leading causes of chronic liver disease and can resulted in liver cirrhosis and hepatocellular carcinoma.According to world health organization,the current HCV infection rate around the world was 0.5%?1%,and about 71 million people arc infectced.However,the mechanism of I-ICV chronic infection is not very clear.Recent years,immune regulation function of vitamin D has demonstrated in various studies.Changes in the level of vitamin D may be associated with HCV infection and liver function.[Objectives]To explore the association of plasma 25-hydroxyvitamin D(25(OH)D)concentration with HCV infection and liver function in paid blood donors.[Methods]In a case-control study,281 participants including 90 patients with chronic hepatitis C,92 HCV natural clearance subjects and 99 healthy controls,were investigated.The subjects' plasma trace elements concentration was detected by inductively coupled plasma mass spectrometry(ICP-MS).The 25(OH)D levels were examined through enzyme linked immunosorbent assay(ELISA).Partial correlation analysis and multivariable logistic regression analysis were used to explore the relationship of plasma 25(OH)D levels and liver function and HCV infection.[Results]The levels of plasma 25(OH)D in chronic HCV infection cases and natural viral clearance subjects were significantly lower than those in controls respectively(all P<0.05).Compared with healthy controls,the level of zinc was decreased,however,the level of iron was increased in patients with chronic HCV infection(all P<0.05).After controlling for age,sex and body mass index(BMI),the HCV viral load was negatively correlated with plasma iron concentration(r=-0.263,P=0.016)and 25(OH)D level(r=-0.276,P=0.Oil).No significant correlations were found between 25(OH)D level and plasma trace elements,concentrations(all P>0.05).The Logistic regression showed that iron was independently associated with the ALT values in patients with persistent HCV infection(OR=1.001,95%CI:1.000-1.002,P=0.030).[Conclusion]Plasma 25(OH)D level and trace elements(Fe,Zn)may be associated with HCV infection outcomes.Especially,iron level is an independent risk factors of chronic HCV infection.Section 2Vitamin D binding protein polymorphisms influence susceptibility to hepatitis C virus infection in a high-risk Chinese population[Background]Hepatitis C Virus(HCV)is one of the most common blood-borne pathogens,which infects about 0.5%?1%of the world population.Individuals infected with HCV exhibit a spcctrum of possible outcomes,including spontaneous clearance,and chronic infection for the majority.Natural progression of viral infection varies dramatically among patients.Explanations of the viral persistence and pathogenesis of HCV have implicated both viral and patient(host)factors.Host immunological and genetic factors could influence the course of the disease.Vitamin D appears to possess potential anti-viral,anti-inflammatory,anti-fibrotic,and immuno-modulatory effects relevant to liver disease(including HCV infection).Vitamin D binding protein(VDBP),binds and transports vitamin D and its metabolite,and influences vitamin D status.Therefore,the VDBP gene polymorphism may be associated with the outcomes of HCV infection.[Objectives]In light of the biological function of vitamin D binding protein(VDBP)in the development and progression of hepatitis C viral(HCV)infection,we hypothesized that genetic variants of VDBP genes were associated with susceptibility to HCV infection.[Methods]We evaluated the association of VDBP genetic polymorphisms with susceptibility to and chronicity of HCV infection in a high-risk Chinese population.Seven single nucleotide polymophisms(SNP)(rs7041,rs222020,rs1155563,rs4588,rs3733359,rs17467825 and rs16847024)in the VDBP gene were genotyped in a case-control study of 886 patients with persistent infection,539 with spontaneous clearance,and 1081 uninfected controls.Binary logistic regression analysis was uscd to assess the effects of these SNPs on HCV infection outcomes.[Results]Two variants rs7041-G(GG vs.TT:adjusted odds ratio(OR)=2.075,95%confidence interval(CI)= 1.384-3.110,P=4.09×10-4;additive model:adjusted OR=1.276,95%CI=1.095-1.488,P=0.002;recessive model:adjusted OR=1.961,95%CI=1.321-2.913,P=0.001)and rs3733359-T(CT vs.CC:adjusted OR=1.328,95%CI=1.090-1.619,P=0.005)alleles were significantly associated with increased susceptibility to HCV infection.The combined effect of unfavorable alleles(rs7041-G and rs3733359-T)was found to be associated with elevated risk of HCV infection in a locus-dosage manner(Ptrend=8.1+6×10-4).Haplotype analysis suggested that,compared with the most frequent haplotype Ars17467825Crs4588Trs7041,the Ars,7467825Crs4588Grs7041 haplotype had an increased susceptibility to HCV infection(adjusted OR=1.202,95%CI=1.016-1.423,P=0.032).[Conclusion]VDBP rs7041-G and rs3733359-T variants may contribute to increased susceptibility to HCV infection in a high-risk Chinese population.