Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization.

Hung, Chin-Chuan; Chang, Wei-Lun; Ho, Jia-Ling; Tai, John Jen; Hsieh, Tsung-Jen; Huang, Hsiao-Ching; Hsieh, Yow-Wen; Liou, Horng-Huei

Hung, Chin-Chuan; Chang, Wei-Lun; Ho, Jia-Ling; Tai, John Jen; Hsieh, Tsung-Jen; Huang, Hsiao-Ching; Hsieh, Yow-Wen; Liou, Horng-Huei.

Afiliación

Hung CC; Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.

Pharmacogenomics ; 13(2): 159-69, 2012 Jan.

Article en En | MEDLINE | ID: mdl-22188362

RESUMEN

AIM: Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs. The aim of the present study is to investigate the impacts of polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of CBZ on the large interindividual variability in dosages and concentrations. METHODS & RESULTS: Genetic polymorphisms in the candidate genes were detected in 234 epileptic patients under maintenance CBZ monotherapy by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant SCN1A IVS5-91G>A and EPHX1 c.337T>C allele tended to require higher CBZ dosages and lower ln(concentration-dose ratios) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher CBZ dosages and lower ln(concentration-dose ratios) (p < 0.0001). In addition, the multiple regression model of concentration-dose ratio of CBZ also revealed that genetic variants in SCN1A, EPHX1 and UGT2B7 genes interactively affect the concentration-dose ratio of CBZ (adjusted r(2) = 55%). CONCLUSION: The present study identified genetic factors associated with CBZ therapy optimization and provided useful information for individualized CBZ therapy in epileptic patients. Further studies in larger populations are needed to confirm our results.

Asunto(s)

Anticonvulsivantes/farmacocinética; Carbamazepina/farmacocinética; Relación Dosis-Respuesta a Droga; Epilepsia/tratamiento farmacológico; Epilepsia/genética; Epóxido Hidrolasas/genética; Glucuronosiltransferasa/genética; Proteínas del Tejido Nervioso/genética; Canales de Sodio/genética; Subfamilia B de Transportador de Casetes de Unión a ATP; Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética; Adulto; Anticonvulsivantes/sangre; Carbamazepina/sangre; Epilepsia/patología; Femenino; Estudios de Asociación Genética; Haplotipos; Humanos; Masculino; Persona de Mediana Edad; Proteína 2 Asociada a Resistencia a Múltiples Medicamentos; Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética; Canal de Sodio Activado por Voltaje NAV1.1; Canal de Sodio Activado por Voltaje NAV1.2; Polimorfismo de Nucleótido Simple

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carbamazepina / Canales de Sodio / Glucuronosiltransferasa / Relación Dosis-Respuesta a Droga / Epilepsia / Epóxido Hidrolasas / Anticonvulsivantes / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Pharmacogenomics Asunto de la revista: FARMACOLOGIA / GENETICA MEDICA Año: 2012 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido

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