title: Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose.
abstract: OBJECTIVE
  To investigate whether the phenprocoumon and acenocoumarol maintenance doses are influenced by genetic variations in GATA-4, a transcription factor of CYP2C9.
  
  
  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.
  
  
  CONCLUSIONS
  Genetic variation in GATA-4 does not seem relevant for clinical implementation.
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Rianne M F
authors.initials: RM
authors.lastname: van Schie
authors.forename: Judith A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: Talitha I
authors.initials: TI
authors.lastname: Verhoef
authors.forename: Tom
authors.initials: T
authors.lastname: Schalekamp
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.forename: Felix J  M
authors.initials: FJ
authors.lastname: van der Meer
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
authors.forename: Martina
authors.initials: M
authors.lastname: Teichert
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Peter N M
authors.initials: PN
authors.lastname: Buhre
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.forename: Anke-Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010644:Phenprocoumon / Q000008:administration & dosage*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics
chemical_list: D000925:Anticoagulants; D050991:GATA4 Transcription Factor; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000074:Acenocoumarol; D010644:Phenprocoumon