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 201.

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Department of Pharmacy

van Schie, R.F.M, Wessels, J.A.M, Verhoef, T.I, Schalekamp, T, le Cessie, S, van der Meer, F.J.M, … Maitland-van der Zee, A-H. (2012). Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose. Pharmacogenomics, 13(16), 1917–1923. doi:10.2217/pgs.12.174