Distribution of genetic polymorphisms associated to Hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population

TRINKS J; CAPUTO M; HULANIUK WOLANIUK ML; BURGOS PRATX L; RÉ V; FORTUNY L; FRÍAS A; TORRES O; NUÑEZ F; GADANO A; CORACH D; FLICHMAN D

Frankfurt

Congreso; The Viral Hepatitis Congress 2013; 2013

Journal of Viral Hepatitis

Single-nucleotide polymorphisms (SNPs) near IL28B and ITPA genes have been described as predictors of response to antiviral treatment and ribavirin induced-hemolytic anemia in HCV patients, respectively. The prevalence of these polymorphisms differs among ethnic groups; however, there is a paucity of information about South American populations. Hence, the aim of this study was to determine the prevalence of these SNPs in the healthy population of different ethnic groups residing in Argentina. DNA samples were obtained from 1287 unrelated anti-HCV [-] volunteers and grouped as follows: i) Argentines (n=951) born in the Pampean region; and ii) immigrants (n=336) from other Latin American countries (178 Bolivians; 88 Paraguayans and 70 Peruvians). SNPs rs1127354C>A (ITPA) and rs12979860C>T (IL28B) were PCR-amplified and characterized by nucleotide sequences. Ethnicity was assessed by analysis of Native American mitochondrial DNA and Y-SNPs (maternal and paternal haplogroups, respectively) using Real Time PCR followed by High Resolution Melting. Fisher's exact test was used for statistical analysis. A p value <0.05 was considered as statistically significant. In regard to IL28B (rs12979860C>T) polymorphism, CC genotype -related to favorable treatment response- was observed in 51.9% of Argentines vs. 35.9% of Bolivians (p<0.0001), 37.1% of Peruvians (p<0.05) and 39.8% of Paraguayans (p<0.05). In regard to ITPA (rs1127354C>A) polymorphisms, CC genotype -related to higher risk of ribavirin induced-hemolytic anemia- was observed in 84.5% of Argentines vs. 98.9% of Bolivians (p<0.0001), 95.7% of Peruvians (p<0.01) and 93.2% of Paraguayans (p<0.01). As regards ancestry, 42.7% of Argentines, 94.6% of Bolivians, 94% of Peruvians and 98% of Paraguayans showed Native American maternal lineages (p<0.0001); whereas, 1% of Argentines, 71% of Bolivians, 40% of Peruvians and 17.9% of Paraguayans showed Native American paternal haplogroups (p<0.002). This is the first systematic study of polymorphisms related to antiviral response in HCV infection and ethnicity characterization in the South American population. There is a significant bias in the distribution of predictive polymorphisms of response to HCV treatment according to the population ancestry. This study highlights the importance of the previous characterization of these variants to evaluate the risk-benefit of antiviral treatment according to the patient ancestry, particularly in a multiethnic and admixed population.