Variation in genes encoding for interferon lambda-3 and lambda-4 in the prediction ofHCV-1 treatment-induced viral clearance

Lydia Giannitrapani, Domenica Gioffreda, Giuseppe Corritore, Antonio M. Ippolito, Michele Milella, Nicola Andriulli, Giovanna D'Andrea, Michele Barone, Teresa Santantonio, Orazio Palmieri, Anna Latiano, Raffaele Cozzolongo, Filomena Morisco, Massimo Fasano, Maurizio Margaglione, Angelo Andriulli, Paolo Tundo, Pietro Gatti, Rosanna Fontana, Maria R. Valvano

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Abstract

Background & Aims: In patients with chronic HCV-1 infection, recent evidencesindicate that determination of a dinucleotide polymorphism(ss469415590, DG/TT) of a new gene, designated IFN lambda-4, might be moreaccurate than the 12979860CC type of the IL28B locus in predicting sustainedvirological response (SVR) following peg-interferon and ribavirin. Inaddition, combined genotyping of different SNPs of the IL28B locus wasshown to help dissect patients most prone to SVR among those withrs12979860CT. We examined whether single or combined genotyping oftwo IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variationmight improve the prediction of SVR. Results: In the study cohort of 539patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, andrs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%).Carriers of either the triplotype rs12979860CC_ss469415590TT/TT_rs8099917TT or the diplotype rs12979860CC_ss469415590TT/TT hadthe highest SVR rate (72%). In carriers of the rs12979860 T allele, neither thers8099917 nor the ss469415590 improved the response prediction. Afterpooling this finding with data from previous studies, in rs12979860 T heterozygousindividuals the co-presence of the rs8099917TT SNP was associatedwith improved response prediction. Conclusion: In HCV-1 patients, thers12979860 polymorphism appeared as the hit SNP better predictingresponse following peg-interferon and ribavirin treatment. Additionalss469415590 or rs8099917 genotyping had no added benefit for response prediction.In the subset of carriers of the rs12979860 T allele, genotyping of thers8099917 SNP was unhelpful in the present investigation, but may informclinical prediction of treatment response when our data were pooled withprevious investigations.
Lingua originaleEnglish
pagine (da-a)1369-1377
Numero di pagine9
RivistaLiver International
Volume34
Stato di pubblicazionePublished - 2013

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All Science Journal Classification (ASJC) codes

  • Hepatology

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Giannitrapani, L., Gioffreda, D., Corritore, G., Ippolito, A. M., Milella, M., Andriulli, N., D'Andrea, G., Barone, M., Santantonio, T., Palmieri, O., Latiano, A., Cozzolongo, R., Morisco, F., Fasano, M., Margaglione, M., Andriulli, A., Tundo, P., Gatti, P., Fontana, R., & Valvano, M. R. (2013). Variation in genes encoding for interferon lambda-3 and lambda-4 in the prediction ofHCV-1 treatment-induced viral clearance. Liver International, 34, 1369-1377.