| ITPA gene variant protects against anemia induced by pegylated interferon-α and ribavirin therapy for Japanese patients with chronic hepatitis C. | |
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MedLine Citation:
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PMID: 20977565 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Naoya Sakamoto; Yasuhito Tanaka; Mina Nakagawa; Hiroshi Yatsuhashi; Shuhei Nishiguchi; Nobuyuki Enomoto; Seishin Azuma; Yuki Nishimura-Sakurai; Sei Kakinuma; Nao Nishida; Katsushi Tokunaga; Masao Honda; Kiyoaki Ito; Masashi Mizokami; Mamoru Watanabe |
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Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Hepatology research : the official journal of the Japan Society of Hepatology Volume: 40 ISSN: 1386-6346 ISO Abbreviation: - Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9711801 Medline TA: Hepatol Res Country: - |
Other Details:
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Languages: ENG Pagination: 1063-1071 Citation Subset: - |
Copyright Information:
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© 2010 The Japan Society of Hepatology. |
Affiliation:
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Department of Gastroenterology and Hepatology Department for Hepatitis Control, Tokyo Medical and Dental University, Tokyo Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya Clinical Research Center, National Nagasaki Medical Center, Nagasaki Department of Internal Medicine, Hyogo College of Medicine First Department of Internal Medicine, University of Yamanashi, Yamanashi Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan. |
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