title: PPARA gene and phenprocoumon: a new predictor of response variability.
abstract: Phenprocoumon is an anticoagulant used for thromboembolic disorder prophylaxis metabolized mainly by CYP3A4. However, polymorphisms in this gene did not explain the observed variability. PPARA (peroxisome proliferator-activated receptor-α) is a nuclear receptor that, among others, influences CYP3A4 gene expression. The aim of this study was to determine whether PPARA gene polymorphisms and the CYP3A4*22 allele are associated with phenprocoumon dose variability. A total of 198 patients on a stable dose of phenprocoumon were included in the study. Genotyping was performed by allele discrimination using standardized TaqMan assays. Differences between the average phenprocoumon dose and genotypes/haplotypes were assessed by analysis of variance and multiple linear regression analyses. Patients with the PPARA rs4253728A allele needed higher phenprocoumon doses. However, the effect size (3%) of this association was small. The CYP3A4*22 allele was not associated with the dose of phenprocoumon. As this is the first report of an association between PPARA gene polymorphisms and phenprocoumon dose, future studies are warranted to confirm these results.
authors.affiliation: aDepartment of Genetics, Federal University of Rio Grande do Sul bRio Grande do Sul Cardiology Institute, Cardiology University Foundation cCardiology Division, Porto Alegre Clinics Hospital, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Botton
authors.forename: Eliane
authors.initials: E
authors.lastname: Bandinelli
authors.forename: Tiago L L
authors.initials: TL
authors.lastname: Leiria
authors.forename: Luis E P
authors.initials: LE
authors.lastname: Rohde
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D010644:Phenprocoumon / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D013923:Thromboembolism / Q000188:drug therapy / Q000235:genetics
chemical_list: D000925:Anticoagulants; D054316:Biomarkers, Pharmacological; D047493:PPAR alpha; D010644:Phenprocoumon