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Variation in genes encoding for interferon λ‐3 and λ‐4 in the prediction of HCV ‐1 treatment‐induced viral clearance
Author(s) -
Palmieri Orazio,
Ippolito Antonio M.,
Margaglione Maurizio,
Valvano Maria R.,
Gioffreda Domenica,
Fasano Massimo,
D'Andrea Giovanna,
Corritore Giuseppe,
Milella Michele,
Andriulli Nicola,
Morisco Filomena,
Giannitrapani Lydia,
Latiano Anna,
Fontana Rosanna,
Gatti Pietro,
Tundo Paolo,
Barone Michele,
Cozzolongo Raffaele,
Santantonio Teresa,
Andriulli Angelo
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12411
Subject(s) - genotyping , snp , ribavirin , locus (genetics) , genotype , snp genotyping , single nucleotide polymorphism , allele , interleukin 28b , typing , medicine , immunology , virology , gene , biology , genetics
Background & Aims In patients with chronic HCV ‐1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/ TT ) of a new gene, designated IFN λ‐4, might be more accurate than the 12979860 CC type of the IL 28B locus in predicting sustained virological response ( SVR ) following peg‐interferon and ribavirin. In addition, combined genotyping of different SNP s of the IL 28B locus was shown to help dissect patients most prone to SVR among those with rs12979860 CT . We examined whether single or combined genotyping of two IL 28B SNP s, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR . Results In the study cohort of 539 patients, 38% had SVR . The SNP s 12979860 CC , rs8099917 TT , and rs469415590 TT / TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860 CC _ss469415590 TT / TT _rs8099917 TT or the diplotype rs12979860 CC _ss469415590 TT / TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co‐presence of the rs8099917 TT SNP was associated with improved response prediction. Conclusion In HCV ‐1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg‐interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations.