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

Rianne M F van Schie; Judith A M Wessels; Talitha I Verhoef; Tom Schalekamp; Saskia le Cessie; Felix J M van der Meer; Frits R Rosendaal; Loes E Visser; Martina Teichert; Albert Hofman; Peter N M Buhre; Anthonius de Boer; Anke-Hilse Maitland-van der Zee

doi:10.2217/pgs.12.174

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

Rianne M F van Schie, Judith A M Wessels, Talitha I Verhoef, Tom Schalekamp, Saskia le Cessie, Felix J M van der Meer, Frits R Rosendaal, Loes E Visser, Martina Teichert, Albert Hofman, Peter N M Buhre, Anthonius de Boer, Anke-Hilse Maitland-van der Zee

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1917-1923
Number of pages	7
Journal	Pharmacogenomics
Volume	13
Issue number	16
DOIs	https://doi.org/10.2217/pgs.12.174
Publication status	Published - Dec 2012

Keywords

Acenocoumarol
Adult
Aged
Aged, 80 and over
Alleles
Anticoagulants
Aryl Hydrocarbon Hydroxylases
Cytochrome P-450 CYP2C9
Female
GATA4 Transcription Factor
Genotype
Humans
Male
Middle Aged
Pharmacogenetics
Phenprocoumon
Polymorphism, Single Nucleotide
Thrombosis

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van Schie, R. M. F., Wessels, J. A. M., Verhoef, T. I., Schalekamp, T., le Cessie, S., van der Meer, F. J. M., Rosendaal, F. R., Visser, L. E., Teichert, M., Hofman, A., Buhre, P. N. M., de Boer, A., & 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. https://doi.org/10.2217/pgs.12.174

@article{3979ce7ddb1243b19e334f9dde7a6f48,

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

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.",

keywords = "Acenocoumarol, Adult, Aged, Aged, 80 and over, Alleles, Anticoagulants, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP2C9, Female, GATA4 Transcription Factor, Genotype, Humans, Male, Middle Aged, Pharmacogenetics, Phenprocoumon, Polymorphism, Single Nucleotide, Thrombosis",

author = "{van Schie}, {Rianne M F} and Wessels, {Judith A M} and Verhoef, {Talitha I} and Tom Schalekamp and {le Cessie}, Saskia and {van der Meer}, {Felix J M} and Rosendaal, {Frits R} and Visser, {Loes E} and Martina Teichert and Albert Hofman and Buhre, {Peter N M} and {de Boer}, Anthonius and {Maitland-van der Zee}, Anke-Hilse",

year = "2012",

month = dec,

doi = "10.2217/pgs.12.174",

language = "English",

volume = "13",

pages = "1917--1923",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Taylor and Francis Ltd.",

number = "16",

}

van Schie, RMF, Wessels, JAM, Verhoef, TI, Schalekamp, T, le Cessie, S, van der Meer, FJM, Rosendaal, FR, Visser, LE, Teichert, M, Hofman, A, Buhre, PNM, de Boer, A & 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, vol. 13, no. 16, pp. 1917-1923. https://doi.org/10.2217/pgs.12.174

TY - JOUR

T1 - Evaluation of the effect of genetic variations in GATA-4 on the phenprocoumon and acenocoumarol maintenance dose

AU - van Schie, Rianne M F

AU - Wessels, Judith A M

AU - Verhoef, Talitha I

AU - Schalekamp, Tom

AU - le Cessie, Saskia

AU - van der Meer, Felix J M

AU - Rosendaal, Frits R

AU - Visser, Loes E

AU - Teichert, Martina

AU - Hofman, Albert

AU - Buhre, Peter N M

AU - de Boer, Anthonius

AU - Maitland-van der Zee, Anke-Hilse

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

KW - Acenocoumarol

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Anticoagulants

KW - Aryl Hydrocarbon Hydroxylases

KW - Cytochrome P-450 CYP2C9

KW - Female

KW - GATA4 Transcription Factor

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Pharmacogenetics

KW - Phenprocoumon

KW - Polymorphism, Single Nucleotide

KW - Thrombosis

U2 - 10.2217/pgs.12.174

DO - 10.2217/pgs.12.174

M3 - Article

C2 - 23215884

SN - 1462-2416

VL - 13

SP - 1917

EP - 1923

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 16

ER -

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

Abstract

Keywords

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