卡马西平
UGT2B7型
药物遗传学
药理学
医学
遗传学
基因型
基因
生物
癫痫
微粒体
精神科
体外
葡萄糖醛酸化
作者
Chin‐Chuan Hung,Wei-Lun Chang,Jia-Ling Ho,John Jen Tai,Tsung-Jen Hsieh,Hsiao‐Ching Huang,Yow‐Wen Hsieh,Horng‐Huei Liou
出处
期刊:Pharmacogenomics
[Future Medicine]
日期:2011-12-21
卷期号:13 (2): 159-169
被引量:69
摘要
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 r2 = 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. Original submitted: 22 July 2011; Revision submitted: 27 September 2011
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