title: Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C.
abstract: Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.
authors.affiliation: Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.
authors.forename: Nathália
authors.initials: N
authors.lastname: Delvaux
authors.affiliation: Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.
authors.forename: Vanessa Duarte da
authors.initials: VD
authors.lastname: Costa
authors.affiliation: Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.
authors.forename: Maristella Matos da
authors.initials: MM
authors.lastname: Costa
authors.affiliation: Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.
authors.forename: Livia Melo
authors.initials: LM
authors.lastname: Villar
authors.affiliation: Departamento de Hepatologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, BR.
authors.forename: Henrique Sérgio Moraes
authors.initials: HS
authors.lastname: Coelho
authors.affiliation: Departamento de Gastroenterologia, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ, BR.
authors.forename: Eliane Bordalo Cathalá
authors.initials: EB
authors.lastname: Esberard
authors.affiliation: Departamento de Gastroenterologia, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ, BR.
authors.forename: Priscila Pollo
authors.initials: PP
authors.lastname: Flores
authors.affiliation: Departamento de Medicina Geral, Hospital Universitário Gaffrée e Guinle, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, BR.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Brandão-Mello
authors.affiliation: Departamento de Hepatologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, BR.
authors.forename: Cristiane Alves
authors.initials: CA
authors.lastname: Villela-Nogueira
authors.affiliation: Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.
authors.forename: Adilson José de
authors.initials: AJ
authors.lastname: Almeida
authors.affiliation: Laboratório de Hepatites Virais, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, BR.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lampe
mesh_terms: D000740:Anemia / Q000139:chemically induced* / Q000235:genetics; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D011755:Pyrophosphatases; D012254:Ribavirin; D000097630:Inosine Triphosphatase