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ITPA gene variant protects against anemia induced by pegylated interferon‐α and ribavirin therapy for Japanese patients with chronic hepatitis C
Author(s) -
Sakamoto Naoya,
Tanaka Yasuhito,
Nakagawa Mina,
Yatsuhashi Hiroshi,
Nishiguchi Shuhei,
Enomoto Nobuyuki,
Azuma Seishin,
NishimuraSakurai Yuki,
Kakinuma Sei,
Nishida Nao,
Tokunaga Katsushi,
Honda Masao,
Ito Kiyoaki,
Mizokami Masashi,
Watanabe Mamoru
Publication year - 2010
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2010.00741.x
Subject(s) - itpa , ribavirin , pegylated interferon , medicine , anemia , gastroenterology , hepatitis c , single nucleotide polymorphism , hemolytic anemia , immunology , hepatitis c virus , genotype , virology , biology , genetics , virus , gene
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.