Genetic polymorphisms of vitamin D pathway predict antiviral treatment outcome in slow responder naïve patients with chronic hepatitis C

Vitamin D serum levels seem to influence antiviral response in chronic hepatitis C. Vitamin D pathway is controlled by genes presenting functional single nucleotide polymorphisms (SNPs). Data regarding the association between these polymorphisms and the rate of sustained viral response (SVR) followi...

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Published in:PloS one 2013-11, Vol.8 (11), p.e80764
Main Authors: Falleti, Edmondo, Cmet, Sara, Fabris, Carlo, Fattovich, Giovanna, Cussigh, Annarosa, Bitetto, Davide, Ceriani, Elisa, Lenisa, Ilaria, Dissegna, Denis, Ieluzzi, Donatella, Rostello, Anna, Pirisi, Mario, Toniutto, Pierluigi
Format: Article
Language:English
Subjects:
25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics
Adult
Alleles
Antiviral agents
Antiviral Agents - therapeutic use
Cholestanetriol 26-Monooxygenase - genetics
Chronic infection
Cytochrome P450 Family 2
Female
Gastroenterology
Genes
Genomes
Genotype & phenotype
Genotypes
Globulins
Hepatitis
Hepatitis C
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - genetics
Hepatitis C, Chronic - metabolism
Humans
Hydroxylase
Interferon
Interferon-alpha - therapeutic use
Internal medicine
Liver
Male
Medicine
Metabolism
Middle Aged
Pathology
Patients
Polyethylene glycol
Polymorphism, Single Nucleotide - genetics
Ribavirin
Ribavirin - therapeutic use
Serum levels
Single-nucleotide polymorphism
Treatment Outcome
Viruses
Vitamin D
Vitamin D - metabolism
Vitamin deficiency
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Summary:Vitamin D serum levels seem to influence antiviral response in chronic hepatitis C. Vitamin D pathway is controlled by genes presenting functional single nucleotide polymorphisms (SNPs). Data regarding the association between these polymorphisms and the rate of sustained viral response (SVR) following antiviral treatment in chronic hepatitis C virus (HCV) infection are largely incomplete. Aim of this study was to evaluate if the carriage of different SNPs of these genes could influence the rate of SVR in patients treated with interferon plus ribavirin. Two hundred and six HCV positive patients treated with PEG-interferon plus ribavirin were retrospectively evaluated. Polymorphic loci rs7041 G>T and rs4588 C>A of the vitamin D transporter GC-globulin, rs10741657 G>A of the vitamin D 25 hydroxylase CYP2R1 and rs10877012 G>T of vitamin D 1-hydroxylase CYP27B1 were genotyped. A genetic model named VDPFA (vitamin D Pathway Functional Alleles) was constructed considering for each patient the sum (from 0 to 8), derived from every functional allele carried, associated with the achievement of SVR. Three groups were identified: those carrying ≤4 VDPFA (N=108), those carrying 5-6 VDPFA (N=78) and those carrying ≥7 VDPFA (N=20). Significant associations were found between the rates of SVR and the VDPFA value both in all (61/108, 53/78, 17/20, p=0.009) and in 1/4-5 HCV genotypes (17/56, 23/43, 6/8, p=0.003). Moreover in patients who don't achieve rapid viral response (RVR) SVR and VDPFA were found to be in stronger associations in all (12/55, 17/39, 7/9, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0080764