Limits...
IFNL4 and IFNL3 associated polymorphisms strongly influence the spontaneous IFN-alpha receptor-1 expression in HCV-infected patients.

Bordi L, Caglioti C, Garbuglia AR, Lapa D, Castilletti C, Taibi C, Capobianchi MR, Lalle E - PLoS ONE (2015)

Bottom Line: Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance.Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4).The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.

ABSTRACT
Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.

Show MeSH

Related in: MedlinePlus

Levels of IFNAR-1 mRNA in PBMC from HCV-infected naїve subjects carrying IFNL4 ss469415590 TT/TT genotype vs patients carrying the ΔG allele.Results are expressed as ratio to beta-actin. The horizontal bar indicates median.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4326132&req=5

pone.0117397.g001: Levels of IFNAR-1 mRNA in PBMC from HCV-infected naїve subjects carrying IFNL4 ss469415590 TT/TT genotype vs patients carrying the ΔG allele.Results are expressed as ratio to beta-actin. The horizontal bar indicates median.

Mentions: The distribution of IFNL3 genotypes was: 8 CC (25%), 13 CT (40.5%), 11 TT (34.5%); the distribution of IFNL4 genotypes was: 18 TT/TT (56.2%), 10 TT/ΔG (31.3%), 4 ΔG/ΔG (12.5%) (Table 1). As shown in Fig. 1, median levels of IFNAR-1 mRNA in PBMC from patients carrying IFNL4 TT/TT were 1,82 fold higher than those from patients carrying the ΔG allele (either TT/ΔG or ΔG/ΔG) [median: 1.026 (IQR: 0.5710–1.420) vs 0.5640 (0.4585–0.9135) p = 0.0053]. No correlation between IFNAR-1 expression and HCV viral load was observed (r = -0.1152; p = 0.6598).


IFNL4 and IFNL3 associated polymorphisms strongly influence the spontaneous IFN-alpha receptor-1 expression in HCV-infected patients.

Bordi L, Caglioti C, Garbuglia AR, Lapa D, Castilletti C, Taibi C, Capobianchi MR, Lalle E - PLoS ONE (2015)

Levels of IFNAR-1 mRNA in PBMC from HCV-infected naїve subjects carrying IFNL4 ss469415590 TT/TT genotype vs patients carrying the ΔG allele.Results are expressed as ratio to beta-actin. The horizontal bar indicates median.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4326132&req=5

pone.0117397.g001: Levels of IFNAR-1 mRNA in PBMC from HCV-infected naїve subjects carrying IFNL4 ss469415590 TT/TT genotype vs patients carrying the ΔG allele.Results are expressed as ratio to beta-actin. The horizontal bar indicates median.
Mentions: The distribution of IFNL3 genotypes was: 8 CC (25%), 13 CT (40.5%), 11 TT (34.5%); the distribution of IFNL4 genotypes was: 18 TT/TT (56.2%), 10 TT/ΔG (31.3%), 4 ΔG/ΔG (12.5%) (Table 1). As shown in Fig. 1, median levels of IFNAR-1 mRNA in PBMC from patients carrying IFNL4 TT/TT were 1,82 fold higher than those from patients carrying the ΔG allele (either TT/ΔG or ΔG/ΔG) [median: 1.026 (IQR: 0.5710–1.420) vs 0.5640 (0.4585–0.9135) p = 0.0053]. No correlation between IFNAR-1 expression and HCV viral load was observed (r = -0.1152; p = 0.6598).

Bottom Line: Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance.Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4).The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.

ABSTRACT
Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.

Show MeSH
Related in: MedlinePlus