Association Of NF-κB Genetic Polymorphisms And Environmental Factors With The HCV Susceptibility Among High-risk Chinese Han Population

Section 1 Analysis of environmental factors on HCV susceptibility in high-risk populationsBackground:Hepatitis C virus(HCV)is mainly transmitted by blood and is is easily transmissible in humans.Dangerous sexual behaviors,dangerous blood exposure(unsafe blood transfusion / donation)and mother to child transmission can increase the risk of HCV infection.In China,the high-risk group of HCV infection is mainly drug users,paid blood donors,and hemodialysis people.In addition to the variability of the virus itself,the environmental factors are also related to the high rate of HCV infection.Aims: To explore the environmental factors associated with hepatitis C infection in high risk populations,and provides new methods and strategies for the prevention of HCV.Methods: This study included 1679 subjects(including 503 drug users and 1176 paid blood donors).By using univariate and stepwise logistic regression analysis,we identified the related environmental factors between drug users and paid blood donors.Results: Gender,drug-intake methods(snorting,injecting)and duration were the relevant factors of HCV infection among the drug users.Furthermore,female(OR=0.408,95%CI: 0.308-0.767)was associated with the decreased risk for HCV infection,while drug injection(OR=8.817,95%CI: 5.577-13.937)and drug-intake duration > 5.5 years(OR=2.891,95%CI:1.824-4.583)were associated with the increased risk for HCV infection.It was found that age,gender,educational background and BMI were the relevant factors of HCV infection among paid blood donors.What’s more,female(OR=3.431,95%CI:2.360-4.988)was associated with the increased risk for HCV infection,while education level beyond elementary school(OR=0.613,95%CI: 0.429-0.876)was associated with the decreased risk for HCV infection amongpaid blood donors.Conclusions: Environmental factors are associated with susceptibility to HCV infection between high risk populations.Female was associated with the decreased risk for HCV infection,while drug injection and drug-intake duration > 5.5 years were associated with the increased risk for HCV infection among the drug users;female was associated with the increased risk for HCV infection,while education level beyond elementary school was associated with the decreased risk for HCV infection among paid blood donors.Section 2 Analysis of NF-κB polymorphism on HCV susceptibility in high-risk populationsBackground: As an important transcription factor,NF-κB plays an important role in cell proliferation,survival,the immediate early virological response,cytokine production,and promoting inflammation.In HCV infection,NF-κB can interact with HCV to affect the outcomes of the disease.This interaction can be different due to the different HCV genotypes.Meanwhile,the variation of host NF-κB pathway can also affect the expression and transcription,regulation of related proteins,thereby affecting the HCV infection process and the prognosis of disease.Aims: To explore the NF-κB polymorphism associated with hepatitis C infection in high risk populations.Methods: This study included 1679 subjects(including 503 drug users and 1176 paid blood donors).By using Taq Man-MGB probe method to analyze the rs72696119 and rs13031237 loci genotypes of NF-κB1 and REL genes,and by using multivariate Logistic regression,we identified related genetic factors between drug users and paid blood donors.To predict the effect of rs72696119 mutation on NFKB1 gene,the secondary structure of RNA was predicted by RNAfold Web Server and Vienna RNA software package 2.4.6.The difference of RNA secondary structure between wild and mutant alleles of NFKB1 rs72696119 was further predicted by minimum free energy.Results: Our study showed that,compared with reference NF-κB1 rs72696119 CC genotype,the carriage of GG genotype was associated with a increased risk of the susceptibility to HCV(OR=1.412,95%CI=1.035-1.927)among the total study population.The minimum free energy of the centroid m RNA secondary structure for mutant allele of rs72696119 was lower than that of wild allele,-34.60 kcal/mol and-54.50 kcal/mol,respectively.The results showed that the energy needed to maintain the structure before and after the mutation of the rs72696119 site was different,so it may affect the binding of transcription factors and the post transcriptional regulation of the NFKB1 gene.It may be a potential molecular mechanism associated with the susceptibility of HCV to the rs72696119 locus.The interaction analysis in the general population showed that there was no interaction between rs72696119 and HCV infection pathway(P=0.200)or gender(P=0.715).There was no significant association between rs13031237 locus and HCV susceptibility in this study.Conclusion: Compared with NF-κB1 rs72696119 CC genotype,the carriage of GG genotype was associated with a increased risk of the susceptibility to HCV among high-risk Chinese Han populations.The mutation of this locus may affect the RNA secondary structure of the gene,so it may affect the binding of transcription factors and the post transcriptional regulation of the NFKB1 gene.It may be a potential molecular mechanism associated with the susceptibility of HCV to the rs72696119 locus.The interaction analysis in the general population showed that there was no interaction between rs72696119 and HCV infection pathway or gender.