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

Abstract

The prevalence of genetic polymorphisms identified as predictors of therapeutic-induced hepatitis C virus (HCV) clearance differs among ethnic groups. However, there is a paucity of information about their prevalence in South American populations, whose genetic background is highly admixed. Hence, single-nucleotide polymorphisms rs12979860, rs1127354 and rs7270101 were characterized in 1350 healthy individuals, and ethnicity was assessed in 259 randomly selected samples. The frequency of rs12979860CC, associated to HCV treatment response, and rs1127354nonCC, related to protection against hemolytic anemia, were significantly higher among individuals with maternal and paternal Non-native American haplogroups (64.5% and 24.2%), intermediate among admixed samples (44.1% and 20.4%) and the lowest for individuals with Native American ancestry (30.4% and 6.5%). This is the first systematic study focused on analyzing HCV predictors of antiviral response and ethnicity in South American populations. The characterization of these variants is critical to evaluate the risk-benefit of antiviral treatment according to the patient ancestry in admixed populations.

Hepatitis C virus pharmacogenomics in Latin American populations: implications in the era of direct-acting antivirals

“…In this region, the high rate of infections with HCV genotype 1 and the high frequency in Native American populations of the TT genotype of IFNL4 SNP rs12979860 – markers associated with poor response to PEG-IFN/RBV therapy in both cases35,75–78 – support the hypothesis that the implementation of IFN-free regimen should be beneficial in terms of cost–benefit. However, before or until global availability to DAAs is achieved, the identification of host predictive markers of antiviral therapy outcome could still be useful, as it will help prioritize DAA access.…”

“…In this regard, recent studies have concluded that the distribution of these SNPs is closely related to the genetic ancestry in Latin America 35,75–78. A study carried out among 2150 non-HCV-infected individuals from Argentina, Peru, Bolivia, and Paraguay, showed that the frequency of IFNL4 and ITPA SNPs exhibits a specific geographical pattern of distribution, even within the same country (Figures 2–4), and is closely related to the maternal and paternal ancestry of the population (Figures 5 and 6).…”

“…A study carried out among 2150 non-HCV-infected individuals from Argentina, Peru, Bolivia, and Paraguay, showed that the frequency of IFNL4 and ITPA SNPs exhibits a specific geographical pattern of distribution, even within the same country (Figures 2–4), and is closely related to the maternal and paternal ancestry of the population (Figures 5 and 6). In fact, the prevalence of favorable genotypes is significantly higher in populations with European ethnicity, intermediate in admixed individuals, and the lowest in populations with Native American ancestry background 75,76. These findings were confirmed in western Mexico, where the TT/GG/ΔG risk haplotype in the IFNL4 gene predominates in Native Americans when compared with the “Mestizos” (admixed) group 35.…”

“…Pharmacogenomics J . 2014;14(6):549–554 75. Adapted with permission from Trinks J, Hulaniuk ML, Caputo M, et al Distribución de polimorfismos de nucleótido simple (SNPs) predictores de la respuesta al tratamiento antiviral en la infección crónica por el virus de la hepatitis C (HCV) en las distintas regiones geográficas de Argentina [Distribution of singlenucleotide polymorphisms (SNPs) predictive of antiviral treatment response in hepatitis C virus (HCV) chronic infection in different geographic regions in Argentina].…”

SVR Rates of HCV-infected population under PEG-IFN-α/R treatment in Northwest China

“…In the United States, the rate of obtaining SVR in the black population is almost 50% less than of white patients, and the probability of obtaining SVR in white patients with HCV genotype 1 treated by PEG-IFN-α/R is approximately 42–53% [7]. In China, the SVR rate was a light higher, could reach 65.3% [8].…”