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Original article

Relationship between polymorphisms of the inosine triphosphatase gene and anaemia or outcome after treatment with pegylated interferon and ribavirin

Masayuki Kurosaki, Yasuhito Tanaka, Keisuke Tanaka, Yuichiro Suzuki, Yoshihide Hoshioka, Nobuharu Tamaki, Tomoji Kato, Yutaka Yasui, Takanori Hosokawa, Ken Ueda, Kaoru Tsuchiya, Teiji Kuzuya, Hiroyuki Nakanishi, Jun Itakura, Yuka Takahashi, Yasuhiro Asahina, Kentaro Matsuura, Fuminaka Sugauchi, Nobuyuki Enomoto, Nao Nishida, Katsushi Tokunaga, Masashi Mizokami, Namiki Izumi

Corresponding author name: Namiki Izumi
Corresponding author e-mail: nizumi@musashino.jrc.or.jp

Citation: Antiviral Therapy 2011; 16:685-694
doi: 10.3851/IMP1796

Date accepted: 28 November 2010
Date published online: 18 May 2011


Background: A genome-wide association study revealed an association between variants of the inosine triphosphatase (ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in combination with other factors.

Methods: Genotype 1b chronic hepatitis C patients (n=132) treated with pegylated interferon (PEG-IFN)-α and RBV for 48 weeks were genotyped for ITPA rs1127354 and examined for anaemia and treatment outcome.

Results: Variants of the ITPA gene protected against severe anaemia throughout the 48-week treatment period and were associated with lower incidence of anaemia-related RBV dose reduction. A combination of the ITPA genotype with baseline haemoglobin (Hb) and creatinine clearance (CLcr) levels predicted severe anaemia with high accuracy (90% sensitivity and 62% specificity). Among a subset of patients with the IL28B genotype of TT at rs8099917, patients with variants of the ITPA gene were associated with a higher rate of receiving >80% of the expected RBV dose, a higher rate of sustained virological response (SVR), and a lower rate of relapse.

Conclusions: The variants of the ITPA gene, which could protect against haemolytic anaemia and RBV dose reduction, were associated with a high rate of SVR by standard PEG-IFN and RBV therapy in a subset of Japanese patients with the favourable TT genotype at rs8099917 of IL28B. A combination of ITPA genetic polymorphisms with baseline Hb and CLcr levels further improves the predictive accuracy of severe anaemia.


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