Effect of CYP2C9, VKORC1, CYP4F2, and GGCX gene variants and patient characteristics on acenocoumarol maintenance dose: Proposal for a dosing algorithm for Moroccan patients

Drug Discoveries & Therapeutics
Abdelhak ElkhazrajiNezha Messaoudi

Abstract

We investigated the impact of non-genetics factors, and single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP4F2, and GGCX on acenocoumarol dosage in Moroccan adult's patients, in order to develop an algorithm to predict acenocoumarol dose for Moroccan patients. Our study consisted of 217 Moroccan patients taking a maintenance dose of acenocoumarol for various indications. The patients were genotyped for VKORC1 -1639 G>A, VKORC1 1173 C>T, CYP2C9*2, CYP2C9*3, CYP4F2 1347 G>A and GGCX 12970 C>G SNPs. The statistical analysis was performed using the SPSS software. The age and SNPs in VKORC1 and CYP2C9 were significantly associated with the weekly acenocoumarol dose requirement (p = 0.023, p = 0.0001 and p = 0.001 respectively). There was no association found between the weekly acenocoumarol dose and the CYP4F2 or GGCX variants (p-value > 0.05). Non-parametric analysis confirmed the accumulate effect of variant alleles at VKORC1 -1639 G>A, VKORC1 1173 C>T and CYP2C9 SNPs on the acenocoumarol dose requirement. With 90.24% less dose required for one patient carrying homozygote variant at VKORC1 -1173 (TT) and CYP2C9 *x/*x haplotype. The multiple linear regression analysis showed that mutation in VKORC1 -1639, VKORC1 1173 SNPs...Continue Reading

References

Sep 1, 1993·The American Journal of Medicine·C S Landefeld, R J Beyth
Aug 15, 2001·Clinical Pharmacology and Therapeutics·R LoebsteinD Ezra
Aug 29, 2001·Clinical Pharmacokinetics·H Takahashi, H Echizen
Mar 14, 2003·European Journal of Clinical Pharmacology·C VerstuyftL Becquemont
Feb 7, 2004·Nature·Tao LiDarrel W Stafford
Apr 30, 2004·Clinical Pharmacology and Therapeutics·Tom SchalekampAnthonius de Boer
Feb 17, 2005·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Simon SandersonJulian Higgins
May 11, 2005·The Pharmacogenomics Journal·M WadeliusP Deloukas
Oct 6, 2005·PLoS Medicine·Pieter H ReitsmaHarry R Büller
May 25, 2006·Bioinformatics·Xavier SoléVíctor Moreno
Oct 19, 2006·Human Genetics·Mia WadeliusPanos Deloukas
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·J OldenburgC R Müller
Sep 4, 2007·Journal of Thrombosis and Haemostasis : JTH·M J RiederA E Rettie
Jan 10, 2008·Clinical Pharmacology and Therapeutics·M-S WenY-T Chen
Feb 6, 2008·Blood·Michael D CaldwellJames K Burmester
Feb 19, 2008·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Monica R McClainJames E Haddow
Nov 21, 2008·Pharmacogenomics·Christos N MarkatosAnthi Travlou
Dec 19, 2009·European Journal of Clinical Pharmacology·Janne CadamuroHannes Oberkofler
Jun 30, 2010·Journal of Thrombosis and Thrombolysis·Joyce H S YouGregory Cheng
Apr 11, 2012·Journal of Clinical Pharmacy and Therapeutics·F Z SmiresS Nadifi
Dec 1, 2012·Thrombosis and Haemostasis·Juan J Cerezo-ManchadoVanessa Roldán
Mar 12, 2013·Thrombosis Research·Dhakchinamoorthi Krishna KumarChandrasekaran Adithan
Jun 9, 2014·Thrombosis Research·Tejasvita GaikwadShrimati Shetty

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May 13, 2021·Pain Practice : the Official Journal of World Institute of Pain·Huawei ChengYancai Sun

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