https://scholars.lib.ntu.edu.tw/handle/123456789/519157
標題: | Association of genetic variants in six candidate genes with valproic acid therapy optimization | 作者: | Hung C.-C. Ho J.-L. Chang W.-L. Tai J.J. Hsieh T.-J. Hsieh Y.-W. HORNG-HUEI LIOU |
公開日期: | 2011 | 卷: | 12 | 期: | 8 | 起(迄)頁: | 1107-1117 | 來源出版物: | Pharmacogenomics | 摘要: | Aims: Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The aim of the study was to investigate whether polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of VPA were associated with the large interindividual variability in dosages and concentrations. Methods & results: Genetic polymorphisms in six candidate genes were detected in 162 epileptic patients under maintenance with VPA monotherapy and stable seizure control by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant UGT1A6 19T>G, 541A>G and 552A>C allele tended to require higher VPA dosages and lower ln(concentration-to-dose ratios [CDRs]) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher VPA dosages and lower lnCDRs (p < 0.0001). On the other hand, carriers of the variant GRIN2B-200T>G allele were more likely to require lower VPA dosages than noncarriers (p < 0.0001) and the homozygous carriers also tended to require lower dosages and higher lnCDRs (p < 0.0001). In addition, the regression model of CDR of VPA also revealed that genetic variants in UGT1A6, GRIN2B and UGT2B7 genes interactively affect CDRs of VPA (adjusted r 2 = 47%). Conclusion: Although there was a limited sample size, the study identified genetic factors associated with VPA therapy optimization that has not been revealed, and provided useful information for individualized VPA therapy in epileptic patients. ? 2011 Future Medicine Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-80051748173&doi=10.2217%2fpgs.11.64&partnerID=40&md5=121ea075e680a2e4f2fd30395b8e11e4 https://scholars.lib.ntu.edu.tw/handle/123456789/519157 |
DOI: | 10.2217/pgs.11.64 | SDG/關鍵字: | fatty acid binding protein 2; glucuronosyltransferase 1A6; glucuronosyltransferase 1A9; glucuronosyltransferase 2B7; n methyl dextro aspartic acid receptor 2B; valproic acid; adult; article; concentration response; controlled study; drug metabolism; epilepsy; female; gene frequency; gene linkage disequilibrium; genetic polymorphism; genetic variability; heterozygosity; homozygosity; human; major clinical study; male; monotherapy; pharmacogenomics; real time polymerase chain reaction; restriction fragment length polymorphism; steady state; temporal lobe epilepsy; Adult; Alleles; Anticonvulsants; DNA; Epilepsy; Epilepsy, Generalized; Female; Gene Frequency; Genetic Variation; Genotype; Heterozygote; Humans; Magnetic Resonance Imaging; Male; Polymorphism, Genetic; Positron-Emission Tomography; Regression Analysis; Reverse Transcriptase Polymerase Chain Reaction; Valproic Acid |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。