IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.

Recent genome-wide association studies report that the SNP rs8099917, located 8.9 kb upstream of the start codon of IL28B, is associated with both disease chronicity and therapeutic response to pegIFN-α and RBV in patients infected with genotype 1 HCV. To determine the effect of rs8099917 variation...

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Autores principales:	Ester Aparicio, Mariona Parera, Sandra Franco, Nuria Pérez-Alvarez, Cristina Tural, Bonaventura Clotet, Miguel Angel Martínez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7aefd52a3c1d43afbf25e84ab29cae08
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spelling	oai:doaj.org-article:7aefd52a3c1d43afbf25e84ab29cae082021-11-18T07:02:41ZIL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.1932-620310.1371/journal.pone.0013771https://doaj.org/article/7aefd52a3c1d43afbf25e84ab29cae082010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21048934/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Recent genome-wide association studies report that the SNP rs8099917, located 8.9 kb upstream of the start codon of IL28B, is associated with both disease chronicity and therapeutic response to pegIFN-α and RBV in patients infected with genotype 1 HCV. To determine the effect of rs8099917 variation on the response of HCV to therapy, we genotyped this variant in a cohort of 160 HCV/HIV-1 coinfected patients in our clinic unit who received combined peg-IFN-α/RBV therapy. The rs8099917 T/G or G/G genotypes were observed in 56 patients (35%). Treatment failure occurred in 80% of G-allele carriers versus 48% of non-carriers (P<0.0001). This result reveals that the G allele was strongly associated with treatment failure in this patient cohort. Importantly, a highly significant association was found between the G-allele and response to therapy in HCV genotype 1-infected patients (P<0.0001) but not in HCV genotype 3-infected patients. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated that the rs8099917 TT genotype was a strong predictor of treatment success (5.83; 1.26-26.92; P = 0.021), independent of baseline plasma HCV-RNA load less than 500 000 IU/ml (4.85; 1.18-19.95; P = 0.025) and absence of advanced liver fibrosis (5.24; 1.20-22.91; P = 0.025). These results reveal the high prevalence of the rs8099917 G allele in HCV/HIV-1 coinfected patients as well as its strong association with treatment failure in HCV genotype 1-infected patients. rs8099917 SNP genotyping may be a valid pre-treatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HIV-infected patients.Ester AparicioMariona PareraSandra FrancoNuria Pérez-AlvarezCristina TuralBonaventura ClotetMiguel Angel MartínezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 10, p e13771 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ester Aparicio Mariona Parera Sandra Franco Nuria Pérez-Alvarez Cristina Tural Bonaventura Clotet Miguel Angel Martínez IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
description	Recent genome-wide association studies report that the SNP rs8099917, located 8.9 kb upstream of the start codon of IL28B, is associated with both disease chronicity and therapeutic response to pegIFN-α and RBV in patients infected with genotype 1 HCV. To determine the effect of rs8099917 variation on the response of HCV to therapy, we genotyped this variant in a cohort of 160 HCV/HIV-1 coinfected patients in our clinic unit who received combined peg-IFN-α/RBV therapy. The rs8099917 T/G or G/G genotypes were observed in 56 patients (35%). Treatment failure occurred in 80% of G-allele carriers versus 48% of non-carriers (P<0.0001). This result reveals that the G allele was strongly associated with treatment failure in this patient cohort. Importantly, a highly significant association was found between the G-allele and response to therapy in HCV genotype 1-infected patients (P<0.0001) but not in HCV genotype 3-infected patients. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated that the rs8099917 TT genotype was a strong predictor of treatment success (5.83; 1.26-26.92; P = 0.021), independent of baseline plasma HCV-RNA load less than 500 000 IU/ml (4.85; 1.18-19.95; P = 0.025) and absence of advanced liver fibrosis (5.24; 1.20-22.91; P = 0.025). These results reveal the high prevalence of the rs8099917 G allele in HCV/HIV-1 coinfected patients as well as its strong association with treatment failure in HCV genotype 1-infected patients. rs8099917 SNP genotyping may be a valid pre-treatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HIV-infected patients.
format	article
author	Ester Aparicio Mariona Parera Sandra Franco Nuria Pérez-Alvarez Cristina Tural Bonaventura Clotet Miguel Angel Martínez
author_facet	Ester Aparicio Mariona Parera Sandra Franco Nuria Pérez-Alvarez Cristina Tural Bonaventura Clotet Miguel Angel Martínez
author_sort	Ester Aparicio
title	IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
title_short	IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
title_full	IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
title_fullStr	IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
title_full_unstemmed	IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
title_sort	il28b snp rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in hcv/hiv-1 coinfected patients.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/7aefd52a3c1d43afbf25e84ab29cae08
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IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.

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