细胞色素氧化酶CYP2A6、CYP2B6和CYP2C9基因多态性对癫痫患者丙戊酸血药浓度的影响。
The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients.
作者信息
Tan Lan, Yu Jin-Tai, Sun Yan-Ping, Ou Jiang-Rong, Song Jing-Hui, Yu Yang
机构信息
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China.
出版信息
Clin Neurol Neurosurg. 2010 May;112(4):320-3. doi: 10.1016/j.clineuro.2010.01.002. Epub 2010 Jan 20.
OBJECTIVES
To investigate influences of the functional polymorphisms of Cytochrome P450 isozymes 2A6 (CYP2A6), 2B6 (CYP2B6), and 2C9 (CYP2C9) on pharmacokinetics of VPA in vivo.
PATIENTS AND METHODS
In the study, we analyzed the genotypes of CYP2A6, CYP2B6, and CYP2C9 and their contribution to the steady-state standardized plasma VPA concentrations in 179 subjects with epilepsy of a Northern Han Chinese population. The genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTS
The subjects with one or two variant CYP2A6*4 alleles showed higher mean plasma VPA concentrations compared with non-4 alleles [(3.4+/-0.4)microg kg ml(-1)mg(-1) vs. (3.6+/-0.4)microg kg ml(-1)mg(-1), p=0.0055]. A significant difference [one-way ANOVA (p=0.0203)] was also found between mean plasma VPA concentrations and the CYP2B6 genotypes. In addition, subjects with the heterozygous genotype CYP2C93 had higher mean plasma VPA concentrations than did those subjects with the wild-type genotype [(3.9+/-0.4)microg kg ml(-1)mg(-1) vs. (3.4+/-0.4)microg kg ml(-1)mg(-1), p=0.0001].
CONCLUSION
The presently evaluated variant alleles in the CYP2A6, CYP2B6, and CYP2C9 genes may explain part of the substantial variability in VPA pharmacokinetics between different subjects.
目的
研究细胞色素P450同工酶2A6（CYP2A6）、2B6（CYP2B6）和2C9（CYP2C9）的功能多态性对丙戊酸（VPA）体内药代动力学的影响。
患者与方法
在本研究中，我们分析了179名中国北方汉族癫痫患者中CYP2A6、CYP2B6和CYP2C9的基因型及其对稳态标准化血浆VPA浓度的影响。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测基因型。
结果
与非4等位基因相比，携带一个或两个CYP2A64变异等位基因的受试者平均血浆VPA浓度更高[（3.4±0.4）μg·kg·ml⁻¹·mg⁻¹对（3.6±0.4）μg·kg·ml⁻¹·mg⁻¹，p = 0.0055]。平均血浆VPA浓度与CYP2B6基因型之间也存在显著差异[单因素方差分析（p = 0.0203）]。此外，CYP2C9*3杂合基因型受试者的平均血浆VPA浓度高于野生型基因型受试者[（3.9±0.4）μg·kg·ml⁻¹·mg⁻¹对（3.4±0.4）μg·kg·ml⁻¹·mg⁻¹，p = 0.0001]。
结论
目前评估的CYP2A6、CYP2B6和CYP2C9基因中的变异等位基因可能解释了不同受试者之间VPA药代动力学存在显著差异的部分原因。
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