ITPA gene variant protects against anemia induced by pegylated interferon-α and ribavirin therapy for Japanese patients with chronic hepatitis C
| Autor: | Yuki Nishimura-Sakurai, Katsushi Tokunaga, Seishin Azuma, Shuhei Nishiguchi, Naoya Sakamoto, Kiyoaki Ito, Masao Honda, Mina Nakagawa, Nobuyuki Enomoto, Nao Nishida, Masashi Mizokami, Hiroshi Yatsuhashi, Sei Kakinuma, Yasuhito Tanaka, Mamoru Watanabe |
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| Rok vydání: | 2010 |
| Předmět: |
Hemolytic anemia
medicine.medical_specialty Hepatology business.industry Anemia Ribavirin Hepatitis C virus Hepatitis C medicine.disease_cause medicine.disease Gastroenterology Virology chemistry.chemical_compound Infectious Diseases chemistry Pegylated interferon Internal medicine Medicine ITPA business Viral load medicine.drug |
| Zdroj: | Hepatology Research. 40:1063-1071 |
| ISSN: | 1386-6346 |
| DOI: | 10.1111/j.1872-034x.2010.00741.x |
| Popis: | Aim: Host genetic variants leading to inosine triphosphatase (ITPA) deficiency, a condition not thought to be clinically important, protect against hemolytic anemia in chronic hepatitis C patients receiving ribavirin. In this study, we evaluated the clinical significance of ITPA variants in Japanese hepatitis C patients who were treated with pegylated interferon plus ribavirin. Methods: In this multicenter retrospective cross-sectional study, 474 hepatitis C patients were enrolled who were treated with pegylated interferon plus ribavirin in four geographically different hospitals in Japan. Patients were grouped according to hemoglobin decline of more than 3 g/dL at week 4. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs6051702, rs1127354) were genotyped. Results: A functional SNP, rs1127354, within the ITPA exon was strongly associated with protection against anemia with only one (0.8%) in 129 patients with the ITPA minor variant A developing severe anemia (P = 5.9 × 10−20). For rs6051702, which had significant association in European-Americans, significant but weak association with severe hemoglobin reduction was found in Japanese (P = 0.009). In patients excluding genotype 1b and high viral load, those with the ITPA minor variant A achieved significantly higher sustained viral response rate than those with the major variant (CC) (96% vs 70%, respectively, P = 0.0066). Conclusion: ITPA SNP, rs1127354, is confirmed to be a useful predictor of ribavirin-induced anemia in Japanese patients. Patients with the ITPA minor variant A (∼27%) have an advantage in pegylated interferon plus ribavirin-based therapies, due to expected adherence of ribavirin doses, resulting in a higher viral clearance rate. |
| Databáze: | OpenAIRE |
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