title: High Prevalence of ITPA Alleles Associated with Ribavirin-Induced Hemolytic Anemia Among Mexican Population.
abstract: The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico.
  
  
  
  In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed.
  
  
  
  The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p &amp;lt; 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p &amp;gt; 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p &amp;lt; 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients.
  
  
  
  A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico.
authors.forename: Karina
authors.initials: K
authors.lastname: Gonzalez-Aldaco
authors.affiliation: Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: João R
authors.initials: JO
authors.lastname: Rebello Pinho
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Panduro
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Martinez-Lopez
authors.affiliation: Departamento de Patologia Clínica e Anatomia Patológica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Ketti
authors.initials: K
authors.lastname: Gleyzer
authors.affiliation: Departamento de Patologia Clínica e Anatomia Patológica, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Nora
authors.initials: N
authors.lastname: Fierro
authors.affiliation: Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico.
authors.forename: Sonia
authors.initials: S
authors.lastname: Roman
mesh_terms: D000328:Adult; D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D000998:Antiviral Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011755:Pyrophosphatases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012254:Ribavirin / Q000009:adverse effects*; D012307:Risk Factors; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D011755:Pyrophosphatases; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
keywords: Direct-acting antivirals; Hepatitis C; Native Amerindians; adverse effects