Prevalence of genetic predictors of response to Hepatitis C virus (HCV) treatment in Buenos Aires city and its suburbs

TRINKS J; HULANIUK WOLANIUK ML; RODRÍGUEZ HERNAEZ J; FORTUNY L; FRÍAS A; TORRES O; NUÑEZ F; GADANO A; FLICHMAN D; ARGIBAY P

Buenos Aires

Jornada; Regional Meeting of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT); 2012

International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT)

Background: HCV can cause chronic hepatitis which may evolve to cirrhosis and hepatocellular carcinoma. Genotype 1-infected patients, the most prevalent in Argentina, achieve sustained virologic response in 46-52% of cases. SNPs (single-nucleotide polymorphisms) around IL28B and ITPA genes have been described as predictors of sustained response and ribavirin induced-hemolytic anemia, respectively. Aim: To determine the prevalence of these SNPs in the healthy population of Buenos Aires city and its suburbs. Materials and Methods: In order to have a representative sample, the number of cases to include was determined by considering the 2010 National Census. Samples of 687 unrelated anti-HCV [-] volunteers were obtained from Buenos Aires city and its suburbs. SNPs rs7270101A>C (ITPA), rs1127354C>A (ITPA), rs12979860C>T (IL28B) and rs8099917T>G (IL28B) were PCR-amplified and the nucleotidic sequences were analyzed to determine the genotype present in each SNP. Results: Samples were grouped as follows: i) Argentines (n=389) born in Buenos Aires city and its suburbs; and ii) immigrants (n=298) born in other Latin American countries (55.7% Bolivia; 25.2% Paraguay; 17.8% Peru; 0.7% Uruguay; 0.3% Dominican Republic and 0.3% Venezuela). In regard to IL28B polymorphisms, CC (rs12979860C>T) and TT (rs8099917T>G) genotypes -related to favorable treatment response- were observed in 56.1% of Argentines vs. 33.7% of Bolivians (p<0.0001), 37.8% of Peruvians (p<0.05) and 43.0% of Paraguayans (p<0.05); whereas, the CT (rs12979860C>T) and TG (rs8099917T>G) genotypes were present in 34.9% of Argentines vs. 47.6% of Bolivians (p<0.01), 47.2% of Peruvians (p=NS) and 47.0% of Paraguayans (p<0.05) and finally, the TT (rs12979860C>T) and GG (rs8099917T>G) genotypes -related to non-response to treatment- were observed in 9.0% of Argentines vs. 18.7% of Bolivians (p<0.0001), 15.1% of Peruvians (p<0.0001) and 10.0% of Paraguayans (p<0.0001). In regard to ITPA polymorphisms, CC (rs1127354C>A) and AA (rs7270101A>C) genotypes -related to higher risk of ribavirin induced-hemolytic anemia- were present in 73.3% of Argentines vs. 94.6% of Bolivians (p<0.0001), 92.4% of Peruvians (p<0.01) and 72.0% of Paraguayans (p=NS). Conclusion: This study highlights the importance of the previous characterization of these variants to evaluate the risk-benefit of antiviral treatment according to the origin of the patient; particularly in a multiethnic population.