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

RMF van Schie; JAM Wessels; TI Verhoef; T Schalekamp; S le Cessie; FJM van der Meer; FR Rosendaal; Loes Visser; Martina Teichert; Bert Hofman; PNM Buhre; A den Boer; AH Zee

doi:10.2217/pgs.12.174

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

RMF van Schie, JAM Wessels, TI Verhoef, T Schalekamp, S le Cessie, FJM van der Meer, FR Rosendaal, Loes Visser, Martina Teichert, Bert Hofman, PNM Buhre, A den Boer, AH Zee

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

7 Citations (Scopus)

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	Undefined/Unknown
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 - 2012

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10.2217/pgs.12.174

http://hdl.handle.net/1765/68588

Cite this

van Schie, RMF., Wessels, JAM., Verhoef, TI., Schalekamp, T., le Cessie, S., van der Meer, FJM., Rosendaal, FR., Visser, L., Teichert, M., Hofman, B., Buhre, PNM., den Boer, A., & Zee, AH. (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

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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.",

author = "{van Schie}, RMF and JAM Wessels and TI Verhoef and T Schalekamp and {le Cessie}, S and {van der Meer}, FJM and FR Rosendaal and Loes Visser and Martina Teichert and Bert Hofman and PNM Buhre and {den Boer}, A and AH Zee",

year = "2012",

doi = "10.2217/pgs.12.174",

language = "Undefined/Unknown",

volume = "13",

pages = "1917--1923",

journal = "Pharmacogenomics",

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van Schie, RMF, Wessels, JAM, Verhoef, TI, Schalekamp, T, le Cessie, S, van der Meer, FJM, Rosendaal, FR, Visser, L, Teichert, M, Hofman, B, Buhre, PNM, den Boer, A & Zee, AH 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, RMF

AU - Wessels, JAM

AU - Verhoef, TI

AU - Schalekamp, T

AU - le Cessie, S

AU - van der Meer, FJM

AU - Rosendaal, FR

AU - Visser, Loes

AU - Teichert, Martina

AU - Hofman, Bert

AU - Buhre, PNM

AU - den Boer, A

AU - Zee, AH

PY - 2012

Y1 - 2012

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.

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DO - 10.2217/pgs.12.174

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EP - 1923

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JF - Pharmacogenomics

SN - 1462-2416

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