Predicción de sensibilidad a la warfarina basada en VKORC1 y CYP2C9 en pacientes de diferentes lugares de Colombia

Abstract

Contribución de los autores:Ricardo A. Cifuentes: concepción del proyecto, genotipificación y análisis de datos Todos los autores participaron en la captación de los pacientes, la recolección de datos, la interpretación de los resultados y la escritura del manuscrito.Predicción de la sensibilidad a la warfarina con base en polimorfismos de los genes VKORC1 y CYP2C9 en pacientes colombianos Introducción. La validación de los factores predictores de la sensibilidad a la warfarina es importante para evitar las hemorragias asociadas con la terapia anticoagulante. En los estudios previos hechos en Colombia con polimorfismos de los genes VKORC1 y CYP2C9, se reportaban algoritmos con rendimientos diferentes para explicar la variación de las dosis, pero no se evaluaba la predicción de la sensibilidad a la warfarina. Objetivo. Determinar la exactitud del análisis farmacogenético de los polimorfismos *2 y *3 en el gen CYP2C9 y 1639G>A en el gen VKORC1 para predecir la sensibilidad a la warfarina en pacientes del Hospital Militar Central, un centro de referencia que atiende pacientes de diferentes lugares de Colombia. Materiales y métodos. Se recopilaron los datos demográficos y clínicos de 130 pacientes que habían recibido una dosis estable de warfarina durante más de dos meses. Se obtuvieron sus genotipos mediante un análisis de curvas de fusión, y, después de verificar el equilibrio de Hardy-Weinberg de los polimorfismos, se hizo un análisis estadístico con enfoque multivariado y predictivo.Resultados. Se construyó un modelo farmacogenético que explicó el 52,8 % de la variación de la dosis (p<0,001), solo 4 % por encima del rendimiento obtenido con los mismos datos usando el algoritmo del International Warfarin Pharmacogenetics Consortium. El modelo predictivo de sensibilidad logró 77,8 % de exactitud e incluyó como factores la edad (p=0,003), los polimorfismos *2 y *3 (p=0,002) y el polimorfismo 1639G>A (p<0,001). Conclusiones. Estos resultados en una población mestiza colombiana respaldan la validez de la predicción de la sensibilidad a la warfarina basada en los polimorfismos de los genes VKORC1 y CYP2C9. Prediction of sensitivity to warfarin based on VKORC1 and CYP2C9 polymorphisms in patients from different places in Colombia Introduction: 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. Materials and methods: Demographic and clinical data were obtained from 130 patients with stable doses of warfari...

Association between polymorphisms of the VKORC1 and CYP2C9 genes and warfarin maintenance dose in Peruvian patients

“…A meta‐analysis by Tang et al ., which encompassed 53 studies, reported that GA and GG carriers required 45% (95% CI 42–49) and 77% (95% CI 70–84) higher doses of warfarin, respectively, compared to homozygous carriers of VKORC1 –1639 AA 16 . Similar findings have been observed in studies conducted in several Latin American countries, including Brazil, 26–29 Colombia 30–32 and Chile, 33 which are consistent with our study.…”

“…higher doses of warfarin, respectively, compared to homozygous carriers of VKORC1-1639 AA. 16 Similar findings have been observed in studies conducted in several Latin American countries, including Brazil, [26][27][28][29] Colombia [30][31][32] and Chile, 33 which are consistent with our study.…”

Frequency of polymorphisms in the CYP2C9, VKORC1, and CYP4F2 genes related to the metabolism of Warfarin in healthy donors from Cali, Colombia

“…These results are consistent with the frequencies found in the VKORC1 promoter, CYP2C9*2, and CYP2C9*3 in patients undergoing Warfarin treatment in Bogota, the capital of Colombia. [19,20] Our findings indicate that despite the slight difference found between these 2 cities, the frequencies of the analyzed alleles were similar.…”

“…The number of patients with heterozygous or homozygous CYP4F2*3 is depicted in superscript. Colombian regions) [20] 112/148 (56. The genetic frequencies of VKORC1*2, CYP2C9*2, CYP2C9*3, CYP4F2*3, and rs12777823 found in our samples are similar to the ones shown for Latin Americans of European and Native American Ancestry and European populations; however, there are distinct differences with Latin Americans of Afro-Caribbean ancestry or African, African American, and South Asian populations (Table 4).…”

“…[12] In the case of Latin America, data are available in Brazil, [13] Peru, [14,15] Puerto Rico, [15,16] Argentina, [15,17] Mexico, [15,18] Cuba, [15] and Colombia. [19,20] Nevertheless, the genetic data reported are usually related to the CYP2C9 gene, and given the multiethnic conformation of Latin–American countries, more data from different populations are needed to capture possible heterogeneities within countries. In this manner, the pharmacogenomic characterization of the Colombian population remains largely unknown.…”