Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients

J Hepatol. 2013 Nov;59(5):964-71. doi: 10.1016/j.jhep.2013.06.030. Epub 2013 Jul 10.

Scherzer TM, Stättermayer AF, Stauber R, Maieron A, Strasser M, Laferl H, Schwarzer R, Datz C, Rutter K, Beinhardt S, Steindl-Munda P, Hofer H, Ferenci P.

Department of Internal Medicine III, Medical University, Vienna, Austria.

Abstract

BACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors, gender differences were analyzed in patients with HCV genotype 1.

METHODS: Hemoglobin levels at baseline (Hb0) and the decline after 4weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n=308, age 43.9±11.1, male:185, female:123, BMI 25.3±3.9, no cirrhosis: n=259, liver cirrhosis: n=49). All patients were treated with 180μg peginterferon-alpha 2a and ribavirin [1000-1200mg/d; females: mean (95% CI) 15.8mg/kg (15.4-16.2); males 14.3 (14.1-14.5); p<0.001]. The SNPs rs6051702, rs1127354, rs7270101 and IL28B rs12979860 were analyzed by the StepOnePlus Real time PCR System.

RESULTS: 188 were major alleles homozygotes; 95 (30.8%) carried the minor allele (C) of rs6051702, 47 (15.3%) of rs1127354 (A), and 69 (22.4%) of rs7270101 (C). The overall Hb0 was 14.8g/dl (14.6-14.9) [mean (95%CI); females 13.7 (13.5-13.9); males 15.5; 15.3-15.6; p<0.001]. The overall HbΔ4 was greater in major allele homozygotes [2.8g/dl (2.6-3.0)] than in minor allele carriers [1.6 (1.4-1.9); p<0.001]. Irrespective of the ITPA genotypes HbΔ4 was smaller in female [2.0 (1.7-2.2)] than in male patients [2.6 (2.4-2.8); p<0.001] and among females in premenopausal [1.5 (1.3-1.8)] than in postmenopausal patients [2.7 (2.3-3.1); p<0.001].

CONCLUSIONS: Irrespective of the protective effect of ITPA mutations, premenopausal females less likely develop ribavirin induced anemia.

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

KEYWORDS: Age, GWAS, Gender, HCV, Hepatitis C virus, ITPA, RVR, Ribavirin-induced anemia, SNP, SVR, genome-wide association study, rapid virologic response, single nucleotide polymorphism, sustained virologic response

PMID: 23850877 [PubMed - in process]

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