Studies Assess Genes in Ribavirin-Induced Anemia

Two variants in the ITPA gene that cause inosine triphosphatase deficiency are linked to protection from ribavirin-induced hemolytic anemia in patients with hepatitis C virus, and a missense substitution on the ITPA gene influences ribavirin-induced anemia in Japanese patients with the virus, according to two studies published in the October issue of Gastroenterology.

THURSDAY, Nov. 4 (HealthDay News) -- Two variants in the ITPA gene that cause inosine triphosphatase (ITPase) deficiency are linked to protection from ribavirin-induced hemolytic anemia in patients with hepatitis C virus (HCV), and a missense substitution on the ITPA gene influences ribavirin-induced anemia in Japanese patients with the virus, according to two studies published in the October issue of Gastroenterology.

In the first study, Alexander J. Thompson, M.D., of the Duke Clinical Research Institute in Durham, N.C., and colleagues analyzed data from 304 patients with genotype 1 HCV who were treated with pegylated interferon and ribavirin. Two ITPA variants were associated with hemoglobin reduction at week four. The minor alleles of each were linked to protection from the reduction. An ITPase deficiency variable -- combining both ITPA variants -- was linked to lower rates of anemia over the 48-week treatment period and a lower rate of ribavirin dose reduction for anemia.

In the second study, Hidenori Ochi, of the RIKEN Center for Genomic Medicine in Hiroshima, Japan, and colleagues analyzed data from 923 patients with HCV-1b also treated with pegylated interferon and ribavirin. They found that hemoglobin decline wasn't correlated with ITPA expression level, indicating that the single nucleotide polymorphism rs1127354 is a single causal variant linked to ribavirin-induced anemia in Japanese patients with HCV.

This research "suggests that rs1127354 would be a useful marker for prediction of ribavirin-induced anemia. Moreover, genetic testing of ITPA variants might be applied to establish personalized dosages in pegylated-interferon and ribavirin combined therapy," Ochi and colleagues conclude.

Several co-authors of the first study disclosed a patent application based on the ITPA discovery. The second study was partly supported by Dainippon Sumitomo Pharma Co. Ltd. and RIKEN.

Abstract - Thompson
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Abstract - Ochi
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