Host genetic,environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus（HBV） infection.The objective of this study was to detect the associations between...Host genetic,environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus（HBV） infection.The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24（ARHGAP24） gene and disease progression of HBV infection in Han Chinese population.These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers,and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers（AsC） in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase.Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase（OR,2.693;95% CI,1.928-3.760;P=6.2×10-9;additive model） and the replication phase（OR,1.490;95% CI,1.104-2.012;P=9.0×10-3;additive model）.These two SNPs were in strong linkage disequilibrium with D＇=0.99 and r2=0.951,and haplotype TT disclosed an increased susceptibility to HBV progression（OR,1.980;95% CI,1.538-2.545;P=8.1×10-8）.These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.展开更多
基金supported by the national basic research program of China (Grant number:No. 2007CB512900)the national natural science foundation of China (Grant number:No. 30872237)
文摘Host genetic,environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus（HBV） infection.The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24（ARHGAP24） gene and disease progression of HBV infection in Han Chinese population.These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers,and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers（AsC） in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase.Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase（OR,2.693;95% CI,1.928-3.760;P=6.2×10-9;additive model） and the replication phase（OR,1.490;95% CI,1.104-2.012;P=9.0×10-3;additive model）.These two SNPs were in strong linkage disequilibrium with D＇=0.99 and r2=0.951,and haplotype TT disclosed an increased susceptibility to HBV progression（OR,1.980;95% CI,1.538-2.545;P=8.1×10-8）.These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.
