Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose. (December 2012)

• Record Type: Journal Article
• Authors: van Schie, Rianne MF; Wessels, Judith AM; Verhoef, Talitha I; Schalekamp, Tom; le Cessie, Saskia; van der Meer, Felix JM; Rosendaal, Frits R; Visser, Loes E; Teichert, Martina; Hofman, Albert; Buhre, Peter NM; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse
• Is Part Of: Pharmacogenomics. Volume 13:Number 16(2012)
• Page Start: 1917
• Page End: 1923
• Publication Date: 2012-12
• Subjects: acenocoumarol -- CYP2C9 -- GATA-4 -- pharmacogenetics -- phenprocoumon; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.12.174
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: To investigate whether the phenprocoumon and acenocoumarol maintenance doses are influenced by genetic variations in GATA-4, a transcription factor of CYP2C9 .Patients & methods: 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.Results: 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.Conclusion: Genetic variation in GATA-4 does not seem relevant for clinical implementation. Original submitted 31 August 2012; Revision submitted 12 October 2012