Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose

• Published in: Pharmacogenomics Vol. 13; no. 16; pp. 1917 - 1923
• Main Authors: van Schie, Rianne M F, Wessels, Judith A M, Verhoef, Talitha I, Schalekamp, Tom, le Cessie, Saskia, van der Meer, Felix J M, Rosendaal, Frits R, Visser, Loes E, Teichert, Martina, Hofman, Albert, Buhre, Peter N M, de Boer, Anthonius, Maitland-van der Zee, Anke-Hilse
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.12.2012
• Subjects: Acenocoumarol - administration & dosage; Adult; Aged; Aged, 80 and over; Alleles; Anticoagulants - administration & dosage; Aryl Hydrocarbon Hydroxylases - genetics; Cytochrome P-450; Cytochrome P-450 CYP2C9; Female; GATA4 Transcription Factor - genetics; Genetic aspects; Genotype; Humans; Male; Middle Aged; Pharmacogenetics; Phenprocoumon - administration & dosage; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Single nucleotide polymorphisms; Thrombosis - drug therapy; Thrombosis - genetics; Transcription factors; Netherlands
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.12.174

To investigate whether the phenprocoumon and acenocoumarol maintenance doses are influenced by genetic variations in GATA-4, a transcription factor of CYP2C9. The influence of seven GATA-4 SNPs on the coumarin maintenance dose was investigated by performing an analysis of variance trend analysis, stratified for CYP2C9 genotypes. Results of the best-explaining SNP were validated in the Rotterdam Study cohort. The largest dose differences were found for rs3735814 in patients using acenocoumarol and having the common allele for CYP2C9. The mean dosages decreased from 2.92 mg/day for the patients having the GATA-4 common alleles to 2.65 mg/day for the patients carrying one GATA-4 variant allele and to 2.37 mg/day for patients carrying two GATA-4 variant alleles (p = 0.004). Results could not be replicated in the validation cohort. For phenprocoumon, no significant effects were observed. Genetic variation in GATA-4 does not seem relevant for clinical implementation.