RGD Reference Report - Influence of ABCB11 and HNF4α genes on daclatasvir plasma concentration: preliminary pharmacogenetic data from the Kineti-C study. - Rat Genome Database

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Influence of ABCB11 and HNF4α genes on daclatasvir plasma concentration: preliminary pharmacogenetic data from the Kineti-C study.

Authors: Cusato, Jessica  De Nicolò, Amedeo  Boglione, Lucio  Favata, Fabio  Ariaudo, Alessandra  Mornese Pinna, Simone  Guido, Federica  Avataneo, Valeria  Carcieri, Chiara  Cariti, Giuseppe  Di Perri, Giovanni  D'Avolio, Antonio 
Citation: Cusato J, etal., J Antimicrob Chemother. 2017 Oct 1;72(10):2846-2849. doi: 10.1093/jac/dkx237.
RGD ID: 14402417
Pubmed: PMID:29091211   (View Abstract at PubMed)
DOI: DOI:10.1093/jac/dkx237   (Journal Full-text)


Background: Daclatasvir is an inhibitor of HCV non-structural 5A protein and is a P-glycoprotein substrate. Pharmacogenetics has had a great impact on previous anti-HCV therapies, particularly considering the association of IL-28B polymorphisms with dual therapy outcome.
Objectives: We investigated the association between daclatasvir plasma concentrations at 2 weeks and 1 month of therapy and genetic variants (SNPs) in genes encoding transporters and nuclear factors (ABCB1, ABCB11 and HNF4α).
Patients and methods: Allelic discrimination was achieved through real-time PCR, whereas plasma concentrations were evaluated through LC-MS/MS.
Results: Fifty-two patients were analysed, all enrolled in the Kineti-C study. HNF4α 975 C > G polymorphism was found to be associated with the daclatasvir plasma concentrations at 2 weeks (P = 0.009) and 1 month of therapy (P = 0.006). Linear regression analysis suggested that, at 2 weeks of therapy, age, baseline BMI and haematocrit were significant predictors of daclatasvir concentrations, whereas at 1 month of therapy ABCB111131 CC and HNF4α CG/GG genotypes were significant predictors of daclatasvir concentrations.
Conclusions: These are the first and preliminary results from our clinical study focusing on daclatasvir pharmacogenetics, showing that this approach could have a role in the era of new anti-HCV therapies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chronic Hepatitis C treatmentIAGP 14402417DNA:SNP:cds:c.1331T>C (rs2287622)(human)RGD 
Chronic Hepatitis C treatmentISOABCB11 (Homo sapiens)14402417; 14402417DNA:SNP:cds:c.1331T>C (rs2287622)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb11  (ATP binding cassette subfamily B member 11)

Genes (Mus musculus)
Abcb11  (ATP-binding cassette, sub-family B member 11)

Genes (Homo sapiens)
ABCB11  (ATP binding cassette subfamily B member 11)


Additional Information