Document Detail

ITPA gene variant protects against anemia induced by pegylated interferon-α and ribavirin therapy for Japanese patients with chronic hepatitis C.
MedLine Citation:
PMID:  20977565     Owner:  NLM     Status:  PubMed-not-MEDLINE    
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.
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:
Type:  Journal Article    
Journal Detail:
Title:  Hepatology research : the official journal of the Japan Society of Hepatology     Volume:  40     ISSN:  1386-6346     ISO Abbreviation:  Hepatol. Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-27     Completed Date:  2012-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9711801     Medline TA:  Hepatol Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1063-71     Citation Subset:  -    
Copyright Information:
© 2010 The Japan Society of Hepatology.
Department of Gastroenterology and Hepatology Department for Hepatitis Control, Tokyo Medical and Dental University, Tokyo, Japan.
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