参与药代动力学/药效学的基因多态性与卡马西平个体化治疗之间的关联
Association between PK/PD-involved gene polymorphisms and carbamazepine-individualized therapy.
作者信息
Ma Chun-Lai, Jiao Zheng, Wu Xun-Yi, Hong Zhen, Wu Zhi-Yuan, Zhong Ming-Kang
机构信息
Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Pharmacogenomics. 2015;16(13):1499-512. doi: 10.2217/pgs.15.94. Epub 2015 Aug 28.
AIM
To evaluate the association between the major genetic variants involved in the pharmacokinetic/pharmacodynamic (PK/PD) properties of carbamazepine (CBZ) and its maintenance doses and concentrations.
PATIENTS & METHODS: The genotypes of 166 patients receiving CBZ monotherapy were detected using high-resolution melting curve (HRM) and TaqMan methods.
RESULTS
Both univariate and multiple regression analyses revealed that carriers of the SCN1A IVS5-91G>A or EPHX1 c.337T>C allele tended to require a higher CBZ dose and a lower CBZ natural logarithmic concentration-dose ratio (lnCDR) than noncarriers (p < 0.05). Furthermore, two interactions between these genes were associated with the lnCDR and the maintenance dosage of CBZ, respectively.
CONCLUSION
SCN1A IVS5-91G>A gene polymorphism is potential genetic biomarker associated with the PK of CBZ.
目的
评估参与卡马西平（CBZ）药代动力学/药效学（PK/PD）特性的主要基因变异与其维持剂量和血药浓度之间的关联。
患者与方法
采用高分辨率熔解曲线（HRM）和TaqMan方法检测166例接受CBZ单药治疗患者的基因型。
结果
单因素和多因素回归分析均显示，SCN1A基因IVS5-91G>A或EPHX1基因c.337T>C等位基因携带者比非携带者往往需要更高的CBZ剂量和更低的CBZ自然对数浓度-剂量比（lnCDR）（p<0.05）。此外，这些基因之间的两种相互作用分别与CBZ的lnCDR和维持剂量相关。
结论
SCN1A基因IVS5-91G>A多态性是与CBZ药代动力学相关的潜在遗传生物标志物。
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