Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

J. A. Nastasi-Catanese, J. R. Padilla-Gutiérrez, Y. Valle, F. Ortega-Gutiérrez, M. P. Gallegos-Arreola, L. E. Figuera

Resultado de la investigación: Contribución a una revistaArtículo

8 Citas (Scopus)

Resumen

Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

Idioma originalInglés
Páginas (desde-hasta)4413-4421
Número de páginas9
PublicaciónGenetics and Molecular Research
Volumen12
N.º4
DOI
EstadoPublicada - 10 oct 2013

Huella dactilar

Acenocoumarol
Mexico
Anticoagulants
Population
Age Factors
Warfarin
Therapeutics
Restriction Fragment Length Polymorphisms
Cytochrome P-450 Enzyme System
Genes
Cytochrome P-450 CYP2C9
Cytochrome P-450 CYP2C19
Regression Analysis
Polymerase Chain Reaction

Citar esto

Nastasi-Catanese, J. A. ; Padilla-Gutiérrez, J. R. ; Valle, Y. ; Ortega-Gutiérrez, F. ; Gallegos-Arreola, M. P. ; Figuera, L. E. / Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response. En: Genetics and Molecular Research. 2013 ; Vol. 12, N.º 4. pp. 4413-4421.
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title = "Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response",
abstract = "Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20{\%} of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.",
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Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response. / Nastasi-Catanese, J. A.; Padilla-Gutiérrez, J. R.; Valle, Y.; Ortega-Gutiérrez, F.; Gallegos-Arreola, M. P.; Figuera, L. E.

En: Genetics and Molecular Research, Vol. 12, N.º 4, 10.10.2013, p. 4413-4421.

Resultado de la investigación: Contribución a una revistaArtículo

TY - JOUR

T1 - Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

AU - Nastasi-Catanese, J. A.

AU - Padilla-Gutiérrez, J. R.

AU - Valle, Y.

AU - Ortega-Gutiérrez, F.

AU - Gallegos-Arreola, M. P.

AU - Figuera, L. E.

PY - 2013/10/10

Y1 - 2013/10/10

N2 - Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

AB - Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

KW - APOE

KW - Acenocoumarol

KW - CYP2C19

KW - CYP2C9

KW - Genetic polymorphisms

KW - PCR-RFLP

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U2 - 10.4238/2013.October.10.7

DO - 10.4238/2013.October.10.7

M3 - Artículo

C2 - 24222221

AN - SCOPUS:84885696467

VL - 12

SP - 4413

EP - 4421

JO - Genetics and Molecular Research

JF - Genetics and Molecular Research

SN - 1676-5680

IS - 4

ER -