60º CONGRESSO BRASILEIRO DE GENÉTICA
26 a 29 de agosto de 2014 Casa Grande Hotel Resort • Guarujá • SP • Brasil
www.sbg.org.br - ISBN 978-85-89109-06-2
PPARA gene polymorphisms are associated with phenprocoumon dose
Mariana R. Botton1; Eliane Bandinelli1; Tiago L. L. Leiria2, Luis E. P. Rohde3; Mara H. Hutz1
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil, 2Instituto de Cardiologia
do Rio Grande do Sul - Fundação Universitária de Cardiologia, Porto Alegre, RS, Brasil 3Divisão de Cardiologia, Hospital de
Clínicas de Porto Alegre, RS, Brazil
1
[email protected]
Keywords: phenprocoumon, PPARA gene, pharmacogenetics
Phenprocoumon is an oral anticoagulant widely used for thromboembolic disorder prophylaxis. Many factors can influence
its effect, like diet, genetic polymorphisms, comedication and demographic characteristics. This oral anticoagulant is
metabolized mainly by CYP3A4 enzyme. However, polymorphisms in this gene did not explain the observed expression
variability. PPARA is a nuclear receptor that, among others, influences CYP3A4 gene expression. The aim of this study was
to determine if rs4253728 and rs4823613 PPARA gene polymorphisms are associated with phenprocoumon dose variation.
A total of 198 patients in phenprocoumon stable dose were included in the present study. Genotyping of rs4253728 and
rs4823613 intronic SNPs were performed by real-time PCR, using standardized TaqMan assays. Differences between average
phenprocoumon dose and haplotypes were assessed by ANOVA. An haplotype containing rs4253728A allele was associated
with higher phenprocoumon dose (P = 0.001). Patients with rs4253728A/rs4823613G (17.05 mg/week) haplotype needed
43% and 15% higher doses than patients with rs4253728G/rs4823613G (11.93 mg/week) and rs4253728G/rs4823613A
(14.83 mg/week) haplotypes, respectively. Our results suggest that patients who have rs4253728A/rs4823613G haplotype
need higher phenprocoumon dose. Since this is the first study to report an association between PPARA gene polymorphisms
and phenprocoumon dose, future studies are warranted to confirm these results in different samples.
Financial support: CNPq. 107