Prediction of sensitivity to warfarin based on VKORC1 and CYP2C9 polymorphisms in patients from different places in Colombia.
BACKGROUND
In the search to prevent hemorrhages associated with anticoagulant therapy, a major goal is to validate predictors of sensitivity to warfarin. However, previous studies in Colombia that included polymorphisms in the VKORC1 and CYP2C9 genes as predictors reported different algorithm performances to explain dose variations, and did not evaluate the prediction of sensitivity to warfarin.


OBJECTIVE
To determine the accuracy of the pharmacogenetic analysis, which includes the CYP2C9 *2 and *3 and VKORC1 1639G>A polymorphisms in predicting patients' sensitivity to warfarin at the Hospital Militar Central, a reference center for patients born in different parts of Colombia.


METHODS
Demographic and clinical data were obtained from 130 patients with stable doses of warfarin for more than two months. Next, their genotypes were obtained through a melting curve analysis. After verifying the Hardy-Weinberg equilibrium of the genotypes from the polymorphisms, a statistical analysis was done, which included multivariate and predictive approaches.


RESULTS
A pharmacogenetic model that explained 52.8% of dose variation (p<0.001) was built, which was only 4% above the performance resulting from the same data using the International Warfarin Pharmacogenetics Consortium algorithm. The model predicting the sensitivity achieved an accuracy of 77.8% and included age (p=0.003), polymorphisms *2 and *3 (p=0.002) and polymorphism 1639G>A (p<0.001) as predictors.


CONCLUSIONS
These results in a mixed population support the prediction of sensitivity to warfarin based on polymorphisms in VKORC1 and CYP2C9 as a valid approach in Colombian patients.
Facultad de Medicina, Universidad Militar Nueva Granada, Bogotá, D.C., Colombia Grupo Insight, Universidad Militar Nueva Granada, Bogotá, D.C., Colombia. ricardo.cifuentesgarcia@gmail.com.
Ricardo A
RA
Cifuentes
Juan
J
Murillo-Rojas
Esperanza
E
Avella-Vargas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003105:Colombia; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D062306:Geography, Medical; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
Pharmacogenetics; algorithms; ethnicity and health; genetic testing; validity of tests; warfarin