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Contribution of ribavirin transporter gene polymorphism to treatment response in peginterferon plus ribavirin therapy for HCV genotype 1b patients
Author(s) -
Tsubota Akihito,
Shimada Noritomo,
Yoshizawa Kai,
Furihata Tomomi,
Agata Rie,
Yumoto Yoko,
Abe Hiroshi,
Ika Makiko,
Namiki Yoshihisa,
Chiba Kan,
Fujise Kiyotaka,
Tada Norio,
Aizawa Yoshio
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02727.x
Subject(s) - ribavirin , itpa , single nucleotide polymorphism , pegylated interferon , medicine , genotype , gastroenterology , snp , hepatitis c virus , virology , interleukin 28b , viral load , odds ratio , hepatitis c , immunology , biology , gene , virus , genetics
Background Standard‐dose ribavirin is crucial for the standard‐of‐care treatment of chronic hepatitis C virus ( HCV ) infection. Equilibrative nucleoside transporter 1 ( ENT 1), encoded by SLC 29A1 gene, is the main transporter that imports ribavirin into human hepatocytes. Aims: To determine whether single nucleotide polymorphisms ( SNP s) at the SLC 29A1 gene could influence the probability of treatment response compared with other baseline and host genetic factors. Methods A total of 526 East Asian patients monoinfected with HCV genotype 1b who had received pegylated interferon alpha plus ribavirin therapy were enrolled in this study. They were assigned randomly to the derivation and confirmatory groups. SNP s related to the IL 28B , ITPA and SLC 29A1 genes were genotyped using real‐time detection polymerase chain reaction. Factors associated with sustained virological response ( SVR ) were analysed using multiple logistic regression analysis. Results Multivariate analysis for the derivation group identified six baseline variables significantly and independently associated with SVR : age [ P = 0.023, odds ratio ( OR ) = 0.97], gender ( P = 0.0047, OR = 2.25), platelet count ( P = 0.00017, OR = 1.11), viral load ( P = 0.00026, OR = 0.54), IL 28B SNP rs12979860 ( P = 1.09 × 10 −7 , OR = 8.68) and SLC 29A1 SNP rs6932345 ( P = 0.030, OR = 1.85). Using the model constructed by these independent variables, positive and negative predictive values and predictive accuracy were 73.3, 70.1 and 71.9% respectively. For the confirmatory group, they were 71.4, 84.6 and 75.3% respectively. The SLC 29A1 and IL 28B SNP s were also significantly associated with rapid virological response. Conclusions The SNP at the major ribavirin transporter ENT 1 gene SLC 29A1 was one of significantly independent factors influencing treatment response, although the impact on the prediction was small.