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.
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 Cpatients 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.
Authors: Nikolaos K Gatselis; Kalliopi Zachou; Asterios Saitis; Maria Samara; George N Dalekos Journal: World J Gastroenterol Date: 2014-03-21 Impact factor: 5.742
Authors: Peter D Simone; Lucas R Struble; Admir Kellezi; Carrie A Brown; Corinn E Grabow; Irine Khutsishvili; Luis A Marky; Youri I Pavlov; Gloria E O Borgstahl Journal: J Struct Biol Date: 2013-03-23 Impact factor: 2.867