Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients

Liang, Ruijuan; Li, Lei; Li, Cuilan; Gao, Yuanfeng; Liu, Wen-ling; Hu, Dayi; Sun, Yaxun

doi:10.1007/s11239-012-0725-7

Cited by 49 publications

(49 citation statements)

References 35 publications

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“…Consistent with our results, Liang et al (2012) found that the AG genotype of VKORC1 -1639G > A SNP was associated with a higher maintenance dose than the AA genotype. D' Andrea et al (2005) also demonstrated that the mean warfarin dose required was higher in patients carrying the CC genotype of VKORC1 1173 compared to patients carrying the CT or TT genotypes.…”

Section: Discussionsupporting

confidence: 91%

VKORC1-1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose

Zhu

Ding

2015

Genetic Testing and Molecular Biomarkers

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Section: Discussionsupporting

confidence: 91%

VKORC1-1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose

Zhu

Ding

2015

Genetic Testing and Molecular Biomarkers

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“…Un ejemplo de ello fue la menor exactitud de predicción del algoritmo del IWPC en una muestra de pacientes egipcios (16). Incluso en grupos étnicos como los han de China, ha sido necesario incluir otras variables predictoras como el gen CYP4F2 (17). La situación se complica en poblaciones muy mezcladas, como la latinoamericana, en la cual la contribución relativa de africanos, amerindios y europeos varía de acuerdo con circunstancias históricas (18).…”

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

2015

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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...

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“…The publication years of the eligible studies ranged between 2009 and 2015. Among the included studies, the majority were of Chinese patients (10)(11)(12)(13)(14)(15)(20)(21)(22)(23)(24)(25). Five studies were of non-Chinese populations (26-30) and one was for an Asian population (31).…”

Section: Resultsmentioning

confidence: 99%

“…However, the findings are inconsistent, particularly for Asian patients (10)(11)(12)(13)(14)(15). In 2012, two results of meta-analyses showed that the CYP4F2 gene polymorphism was associated with the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis XUE SUN 1,2 , WAN-YING YU 1,2 , WAN-LE MA 1 , LI-HUA HUANG 3 and GUO-PING YANG warfarin maintenance dosage (16,17).…”

Section: Introductionmentioning

confidence: 99%

Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis

Sun

et al. 2016

Biomedical Reports

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Abstract.Warfarin is an oral anticoagulant with significant interpatient variability in dosage. A large number of studies have confirmed that the individual warfarin dose is mainly affected by the cytochrome P450 complex subunit 2C9 and vitamin K epoxide reductase complex subunit 1. However, the association between cytochrome P450 4F2 (CYP4F2) gene polymorphisms and warfarin dosage in the Asian population remains controversial. To investigate the impact of the CYP4F2 polymorphism rs2108622 (p.V433M) on warfarin dose requirement, a systematic review and meta-analysis were conducted. According to the strict inclusion and exclusion criteria set, a comprehensive literature search was performed, and the studies published before August 5, 2015 were searched for in PubMed, EMBASE and the China National Knowledge Infrastructure databases. The references were checked by two independent reviewers. The association between the warfarin maintenance dose and CYP4F2 polymorphism was analyzed. Twenty-two studies were included in the meta-analysis. Compared with the CYP4F2 genotype CC, carriers of the CT and TT genotypes required a 9 [95% confidence interval (CI): 6.0-13.0] and 20% (95% CI, 13.0-27.0) higher warfarin dose, respectively. In the combined analysis, T carriers (CT+TT) required an 11% (95% CI, 8.0-14.0) higher warfarin dose compared to the CC genotype. In addition, there was a 10% (95% CI, 5.0-15.0) higher warfarin dose in TT carriers compared to the CT genotype (all P<0.05). The results of the meta-analysis suggest that the effects of the CYP4F2 polymorphism on individual warfarin dose have a statistically significant difference, and the effect degree is variable in the subgroups. Further studies are expected to explore whether the pharmacogenetics model including the CYP4F2 polymorphism can strengthen the prediction of warfarin dose. IntroductionWarfarin is a commonly oral anticoagulant, mainly used clinically in the treatment of thromboembolic diseases, such as atrial fibrillation (AF) and deep venous thrombosis (DVT); however, the existence of high interpatient variability in drug dosage may increase the risk of bleeding or thrombosis. Studies indicated that individual warfarin dose was influenced by a host of factors, including genetic and environmental factors. Genetic factors are one of the main reasons for the individual difference in warfarin maintenance dosage. Previous studies have also suggested that cytochrome P450 complex subunit 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms, age, weight and body surface area can explain ~50% of the influence on warfarin dose requirement (1-6). Therefore, there remains a 50% uncertainty of the other factors to be further explored.The cytochrome P450 4F2 (CYP4F2) gene, consisting of 13 exons and 12 introns and encoding 520 amino acid residues, is located on chromosome 19p13.12 in humans. Studies have shown that there are numerous single-nucleotide polymorphisms (SNPs) in the CYP4F2 gene open reading frame, such as rs2108622, rs2074...

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Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients

Cited by 49 publications

References 35 publications

VKORC1-1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose

VKORC1-1639G/A and 1173 C/T Genetic Polymorphisms Influence Individual Differences in Warfarin Maintenance Dose

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

Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis

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