Association Of Chemokine CXC Subfamily Gene Polymorphism With HCV Spontaneous Clearance And Therapeutic Response

Section 1The association of chemokine CXC subfamily gene polymorphisms with HCV spontaneous clearance among high risk population[Backgrounds]Currently,about 1%-3%people have infected hepatitis C virus all over the world.Hepatitis C virus(HCV)is eliminated from the host in approximately 75%-80%of persistent HCV individuals.Chemokine CXC subfamily play a vital role during the infection of hepatitis C virus,few studies have examined the relation between the genetic variants of the genes and outcomes of HCV.[Objectives]This study aims to explore the association of CXCR2,CXCR6,CXCL9,CXCL10 and CXCL12 polymorphisms with the outcome of HCV infection,and provide scientific evidences for disease control and clinical treatment.[Methods]The case-control study included 1001 persistent HCV cases and 599 spontaneous clearance cases,seven SNPs of gene CXCR2,CXCR6,CXCL12,CXCL9 and CXCL10 were genotyped by Taqman-MGB probe technology to assess their association with HCV spontaneous clearance.We used Stata 12.0 software to analyze the all database.[Results]In drug users,hemodialysis patients and former paid-blood donors,mutant T allele of CXCR6 rs2234358 was more likely to clear HCV virus in the dominant and additive models.The adjusted OR was 1.50(1.16-1.96),and 1.33(1.08-1.65),respectively,mutant C allele of CXCR2 rs1126579 was more susceptible to persistent infection(dominant model:adjusted OR=0.78,95%CI=0.63-0.97;additive model:adjusted OR=0.85,95%CI=0.72-0.99).The combined effects of rs2234358-T and rs1126579-T were analyzed in Cochran-Armitage’s trend test.There was a decreased risk of persistent infection with the more favorable genotypes,subjects carrying 3-4 favorable genotypes was more likely to clear HCV virus(OR=2.64,95%CI=1.62-4.29).Stepwise regression analysis showed that AST,rs 1126579,age and rs2234358 were the independent predictive factors of chronic HCV infection,the area under the ROC curve was 0.7392.[Conclusion]The single nucleotide polymorphism of CXCR2 rs1126579 and CXCR6 rs2234358 are associated with HCV spontaneous clearance.AST,rsl 126579,rs2234358 and age are also related to the outcome of HCV infection.However,further studies are needed to confirm our result.Section 2The association of chemokine CXC subfamily gene polymorphisms with therapeutic response among chronic hepatitis C patients[Backgrounds]HCV poses a serious global health problem due to its adverse clinical outcones,such as cirrhosis and hepatocellular carcinoma.Treatment for chronic hepatitis C consists of interferon(IFN)plus ribavirin(RBV)and protease inhibitors such as telaprevir and boceprevir.The influence of host gene polymorphisms has attracted attention in recent years.Chemokine CXC subfamily play an important role during the treatment.[Objectives]The aim of this study is to determine the association of CXCR2,CXCR6,CXCL9,CXCL10 and CXCL12 polymorphisms with virological response among chronic hepatitis C patient in Chinese Han population and establish the effect prediction model.[Methods]A total of 282 cases of patients who completed the course of treatment were included.HCV viral load and clinical parameters of baseline and 4,12,24,48 weeks and 24 weeks after treatment were collected.Genotyping of CXCR2,CXCR6,CXCL9,CXCL10 and CXCL12 gene polymorphism was performed using Taqman-MGB probe technology.We used Stata 12.0 software to analyze the association of the distribution of genotypes with virological response.[Results]A total of 282 cases of patients were enrolled in the study,180(63.8%)CHC patients achieved SVR.The SVR rate in carriers of CXCR2 rs 1126579 TT genotype,CT variants and CC patients were 72.36%,63.20 and 35.29%.Mutant C allele of CXCR2 rs1126579 was likely to decrease SVR rate(dominant model:adjusted OR=0.57,95%CI=0.32-0.99;recessive model:adjusted OR=0.24,95%CI=0.10-0.56;additive model:adjusted OR=0.52,95%CI=0.35-0.79).The SVR rate(77.56%)was higher in carriers of CXCR6 rs2234358 TT genotype,and 69.60%for those carrying the GT variants,only 50.93%for GG patients,mutant T allele of CXCR6 rs2234358 possibly could increase SVR rate in our study.The adjusted ORs and 95%CI were 2.20(1.25-3.86),1.77(1.17-2.68)in dominant and additive models,respectively.The combined effects of rs2234358-T and rs1126579-T were analyzed in Cochran-Armitage’s trend test.There was an increased risk of SVR with the more favorable genotypes(P<0.001).Stepwise regression analysis showed that only AFP and rs223 43 5 8 were independent predictive factors of SVR,the area under the ROC curve is 0.6609.With the advancement of the treatment,HCV RNA negative rate increased gradually and fell down at the end of the treatment.HCV RNA negative rate in patients CXCR6 rs2234358 GT and TT,CXCR2 rs1126579 TT were higher than another group.[Conclusion]CXCR2 rs1126579 and CXCR6 rs2234358 are associated with SVR of pegylated interferon and ribavirin treatment,only AFP and rs2234358 are independent factors of SVR.However,further studies are needed to confirm our result.