title: The recipient CYP2D6 allele 4-associated poor metabolizer status correlates with an early fibrosis development after liver transplantation.
abstract: CYP2D6 is part of the cytochrome P450 system, which catalyzes biotransformation of endogenous substrates and xenobiotics. Approximately 10% of the Caucasian population has two null alleles, resulting in a poor metabolizer (PM) status. Mostly, allele four (CYP2D6*4) is responsible for the PM status, which is suspected to be associated with an accelerated fibrosis progression (FP). The aim of the present study was to analyze the role of the CYP2D6*4 genotype for FP after liver transplantation (LT). Genotypes were determined in liver biopsies (donor) and peripheral blood (recipient) by fluorescence resonance energy transfer. Data were correlated with clinical variables and risk factors for fibrosis. We analyzed 517 LTs performed between 1997 and 2009. Overall donor and recipient allele frequencies were comparable (18.0%, 20.5%; P = 0.43). The donor genotype did not correlate with FP. In contrast, recipients carrying CYP2D6*4, showed a significant higher risk for an accelerated FP (P = 0.011) in HCV positive (P = 0.038) and HCV negative patients (P = 0.033). Results were confirmed by multivariate analysis (Hazard ratio 1.65; P = 0.001). The CYP2D6*4-associated PM status of the donor liver seems to have no influence on FP after LT. Recipients, carrying the allele, have an elevated risk for an accelerated FP.
authors.affiliation: 1st Department of Medicine, University of Mainz, Mainz, Germany. tim.zimmermann@unimedizin-mainz.de
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Maria
authors.initials: M
authors.lastname: Hoppe-Lotichius
authors.forename: Andreas
authors.initials: A
authors.lastname: Körner
authors.forename: Anja
authors.initials: A
authors.lastname: Lautem
authors.forename: Michael
authors.initials: M
authors.lastname: Heise
authors.forename: Daniel
authors.initials: D
authors.lastname: Foltys
authors.forename: Nina
authors.initials: N
authors.lastname: Weiler
authors.forename: Stefan
authors.initials: S
authors.lastname: Biesterfeld
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Gerd
authors.initials: G
authors.lastname: Otto
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000601:surgery; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000235:genetics; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D019389:Cytochrome P-450 CYP2D6