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Role of CYP4F2, CYP2C19, and CYP1A2 polymorphisms on acenocoumarol pharmacogenomic algorithm accuracy improvement in the Greek population: need for sub-phenotype analysis

Role of CYP4F2, CYP2C19, and CYP1A2 polymorphisms on acenocoumarol pharmacogenomic algorithm... AbstractBackground:We have earlier developed a pharmacogenomic algorithm for acenocoumarol dose prediction in Greek patients that included CYP2C9/VKORC1 genetic information. This study aims at analyzing the potential effect of CYP4F2, CYP2C19, and CYP1A2 gene polymorphisms on acenocoumarol dose requirements and at further improving the Greek-specific pharmacogenomic algorithm.Methods:A total of 205 Greek patients taking acenocoumarol (140 who reached and 65 who did not reach stable dose), participants of acenocoumarol EU-PACT trial, were included in the study. CYP4F2, CYP2C19, and CYP1A2 polymorphisms were genotyped by use of the PCR-RFLP method. All patients were previously genotyped for CYP2C9/VKORC1 polymorphisms.Results:In the pooled sample, CYP4F2, CYP2C19, and CYP1A2 polymorphisms do not affect independently acenocoumarol dose requirements. For CYP4F2, significant effects were found on patients’ ability to reach stable dose and on acenocoumarol dose requirements when CYP2C9/VKORC1 sub-phenotypes were analyzed. Specifically, when the patients were stratified according to their CYP2C9/VKORC1 functional bins, in sensitive responders, CYP4F2*3 allele carriers (CYP4F2 *1/*3 and *3/*3 genotypes) were more frequent in the patient group who reached stable dose (p=0.049). Additionally, in CYP2C9 intermediate metabolizers (IMs), after adjusting for age, weight, and VKORC1 genotypes, CYP4F2 genotypes were significantly associated with acenocoumarol stable dose (β: 0.07; 95% CI: 0.006–0.134; p=0.033).Conclusions:CYP4F2 gene shows a prominent weak association with acenocoumarol dose requirements. Sub-phenotype analysis is potentially important in determining additional gene polymorphisms that are associated with acenocoumarol dose requirements. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Metabolism and Drug Interactions de Gruyter

Role of CYP4F2, CYP2C19, and CYP1A2 polymorphisms on acenocoumarol pharmacogenomic algorithm accuracy improvement in the Greek population: need for sub-phenotype analysis

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References (43)

Publisher
de Gruyter
Copyright
©2017 Walter de Gruyter GmbH, Berlin/Boston
ISSN
2191-0162
eISSN
2363-8915
DOI
10.1515/dmpt-2017-0034
pmid
29252193
Publisher site
See Article on Publisher Site

Abstract

AbstractBackground:We have earlier developed a pharmacogenomic algorithm for acenocoumarol dose prediction in Greek patients that included CYP2C9/VKORC1 genetic information. This study aims at analyzing the potential effect of CYP4F2, CYP2C19, and CYP1A2 gene polymorphisms on acenocoumarol dose requirements and at further improving the Greek-specific pharmacogenomic algorithm.Methods:A total of 205 Greek patients taking acenocoumarol (140 who reached and 65 who did not reach stable dose), participants of acenocoumarol EU-PACT trial, were included in the study. CYP4F2, CYP2C19, and CYP1A2 polymorphisms were genotyped by use of the PCR-RFLP method. All patients were previously genotyped for CYP2C9/VKORC1 polymorphisms.Results:In the pooled sample, CYP4F2, CYP2C19, and CYP1A2 polymorphisms do not affect independently acenocoumarol dose requirements. For CYP4F2, significant effects were found on patients’ ability to reach stable dose and on acenocoumarol dose requirements when CYP2C9/VKORC1 sub-phenotypes were analyzed. Specifically, when the patients were stratified according to their CYP2C9/VKORC1 functional bins, in sensitive responders, CYP4F2*3 allele carriers (CYP4F2 *1/*3 and *3/*3 genotypes) were more frequent in the patient group who reached stable dose (p=0.049). Additionally, in CYP2C9 intermediate metabolizers (IMs), after adjusting for age, weight, and VKORC1 genotypes, CYP4F2 genotypes were significantly associated with acenocoumarol stable dose (β: 0.07; 95% CI: 0.006–0.134; p=0.033).Conclusions:CYP4F2 gene shows a prominent weak association with acenocoumarol dose requirements. Sub-phenotype analysis is potentially important in determining additional gene polymorphisms that are associated with acenocoumarol dose requirements.

Journal

Drug Metabolism and Drug Interactions – de Gruyter

Published: Dec 20, 2017

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