https://scholars.lib.ntu.edu.tw/handle/123456789/519186
標題: | A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose | 作者: | Tate S.K. Singh R. Hung C.-C. Tai J.J. Depondt C. Cavalleri G.L. Sisodiya S.M. Goldstein D.B. HORNG-HUEI LIOU |
公開日期: | 2006 | 卷: | 16 | 期: | 10 | 起(迄)頁: | 721-726 | 來源出版物: | Pharmacogenetics and Genomics | 摘要: | OBJECTIVES: A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A gene (one of the genes encoding the drug target) has been previously associated with maximum dose of phenytoin used clinically, and also maximum dose of carbamazepine, another antiepileptic drug with the same drug target. METHODS: We have related variation at the SCN1A IVS5-91 G>A polymorphism to maximum dose and to maintenance dose of phenytoin in 168 patients with epilepsy treated with phenytoin. We also related genotype to phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We genotyped the polymorphism using an Applied Biosystems Taqman assay. RESULTS: The polymorphism is associated with phenytoin serum concentration at maintenance dose (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this association is also significant (P=0.03). Neither association remains significant after Bonferroni correction for multiple testing. CONCLUSIONS: These results are not a replication of the original study. They do, however, support the hypothesis that this polymorphism influences the clinical use of phenytoin. They also demonstrate the utility of using multiple phenotypes in pharmacogenetics studies, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is particularly useful to obtain data on serum levels in addition to dose because association of a pharmacodynamic variant may be stronger with serum levels than dose as the serum level may eliminate or reduce pharmacokinetic variability. ? 2006 Lippincott Williams & Wilkins. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33749037686&doi=10.1097%2f01.fpc.0000230114.41828.73&partnerID=40&md5=24c62d667976905754730b4b02f5fa22 https://scholars.lib.ntu.edu.tw/handle/123456789/519186 |
DOI: | 10.1097/01.fpc.0000230114.41828.73 | SDG/關鍵字: | carbamazepine; clonazepam; gabapentin; lamotrigine; phenobarbital; phenytoin; sodium channel; sodium channel SCN1A; topiramate; unclassified drug; valproic acid; vigabatrin; analytic method; article; bioassay; clinical medicine; cohort analysis; controlled study; drug blood level; drug effect; drug metabolism; drug use; epilepsy; female; genetic association; genetic polymorphism; genetic variability; genotype; human; hypothesis; maintenance drug dose; major clinical study; male; pharmacogenetics; phenotype; priority journal; statistical significance; Anticonvulsants; Base Sequence; DNA Primers; Female; Humans; Male; Nerve Tissue Proteins; Phenytoin; Polymorphism, Genetic; Sodium Channels |
顯示於: | 醫學系 |
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