Logotipo del SMU

RMU

Uruguayan Medical Journal

ISSN: 1688-0390


Vol.24 - Nº 4 - Dic. 2008

Previous Art | Index | Next Art

Effects of VKORC1 and CYP2C9 gene genotypes in Individual response to warfarin

ESPERON P; RAGGIO V; GOYENECHE L; LORENZO M; TAUB I; STOLL M
Rev Med Urug 2008; 24: 266-276
Full text (spanish) |  Full text (spanish) (New windows, pdf) | Abstract

Abstract

Introduction: warfarin is a widely used oral anticoagulant.

Its narrow therapeutic range (NTR) and its large interindividual variability requires strict control when administered to avoid hemorrhagic accidents.

Objectives: to correlate CYP2C9*2 and *3 and VKORC1 (C1173T) genetic variants with response and adverse side effects.

Method: CYP2C9*1, *2, *3, and VKORC1 genotypes were obtained by a commonly used PCR-RFLP procedure.

The results were analyzed using SPSS 12.0. statistical package.

Results: there is a tendency to reduce the dosage in connection with the presence of polymorphic alleles.

CYP2C9*3 carriers require the lower maintenance dosage, followed by CYP2C9*2 carriers and then by CYP2C9 *1 homozygotes (4.4±1.0 versus 5.4±2.3 versus 7.0±3.6 mg/ d, p=0.03). CYP2C9*3 carriers also showed an increase in the anticoagulation risk, which required almost twice the number of dose adjustments to achieve appropriate anticoagulation.

As to VKORC1, T/T homozygotes needed the lowest dose, followed by the C/T heterozygotes, and then by the C/C homozygotes (3.6±0.6 versus 5.5±0.5 and 7.9±0.7 mg/d, p <0,001). Risk of overcoagulation was higher in T/T patients than in C/T or C/C patients. T/T genotype of VKORC1 causes a decrease of nearly 50% in the warfarine daily dosage for all combinations with CYP2C9.

Conclusions: we confirmed an increased sensitivity to warfarine in patient carriers of *2 and *3 CYP2C9 alleles and T VKORC1 alleles. We showed a combined effect (approximately accumulative) of variant alleles in both genes.