Prevalence of IFNL3 gene polymorphism among blood donors and its relation to genomic profile of ancestry in Brazil

Abstract

The recent development of interferon-free regimens based on direct-acting antivirals for the treatment of chronic hepatitis C virus infection has benefited many but not all patients. Some patients still experience treatment failure, possibly attributed to unknown host and viral factors, such as IFNL3 gene polymorphism. The present study assessed the prevalence of rs12979860-CC, rs12979860-CT, and rs12979860-TT genotypes of the IFNL3 gene, and its relationship with ancestry informative markers in 949 adult Brazilian healthy blood donors. Race was analyzed using ancestry informative markers as a surrogate for ancestry. IFNL3 gene was genotyped using the ABI TaqMan single nucleotide polymorphisms genotyping assays. The overall frequency of rs12979860-CC genotype was 36.9%. The contribution of African ancestry was significantly higher among donors from the northeast region in relation to southeast donors, whereas the influence of European ancestry was significantly higher in southeast donors. Donors with rs12979860-CC and rs12979860-CT genotypes had similar ancestry background. The contribution of African ancestry was higher among rs12979860-TT genotype donors in comparison to both rs12979860-CC and rs12979860-CT genotypes. The prevalence of rs12979860-CC genotype is similar to that found in the US, despite the Brazilian ancestry informative markers admixture. However, in terms of ancestry, rs12979860-CT genotype was much closer to rs12979860-CC individuals than to rs12979860-TT.

Association between IFNGR1 gene polymorphisms and tuberculosis susceptibility: A meta-analysis

“…Gene polymorphisms are complicated and fluctuating, especially among different ethnicities and populations from different regions ( 41 – 43 ). Studies have revealed that discrepancy in distribution of IFNGR1 genotype may exist in different populations ( 44 ), which may contribute to the inconsistent associations of genetic polymorphisms with TB susceptibility.…”

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“…Several studies have reported the distribution of the rs12979860 genotypes in different populations, mainly assessing its correlation with the susceptibility to different viral infections and response to antiviral treatments (Wu et al, 2012;Porto et al, 2015;Taheri et al, 2015;Echeverría et al, 2018). The correlation of this distribution and the local ancestry of these populations as well as its implications have also been assessed (Indolfi et al, 2014b;Rizzo et al, 2016), though this is the first report in an Argentinean global population. The overall distribution of rs12979860-CC, CT and TT was 29.17%, 50.0% and 20.83%, respectively.…”

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha

“…In this study, we also evaluated SNPs in the IFNL3/4 region among Brazilians, an admixed population of three paternal lineages consisting of Native-American, European and African ancestries. Other studies with CHC patients treated with Peg-IFN-α/Ribavirin from different regions in Brazil focused on the SNPs rs12979860 and rs8099917, evidencing that CC and TT genotypes, respectively, presented favorable treatment outcomes ( Ge et al., 2009 ; Thomas et al., 2009 ; Cavalcante et al., 2012 ; Ramos et al., 2012 ; Moreira et al., 2016 ; Rizzo et al., 2016 ). Here, we confirmed the association of several SNPs with the responsiveness for treatment, highlighting the rs12979860 as the strongest predictor in obtaining SVR in patients treated with Peg-IFNα.…”