CYP2A6基因多态性对丙戊酸钠血药浓度的影响

Effect of CYP2A6 genetic polymorphisms on serum concentration of sodium valproate

目的探讨细胞色素P4502A6(CYP2A6)基因多态性对丙戊酸钠血药浓度的影响。方法选择单药服用丙戊酸钠的癫患者98例,应用巢式PCR(nested-primerpolymerasechainreaction)方法分析其CYP2A6基因型,分析等位基因CYP2A6*1及CYP2A6*4;同时应用荧光偏振免疫法(FPIA)测定患者丙戊酸钠的血药浓度。结果98例患者中CYP2A6基因型为*1/*1者73例(74·5%),*1/*4者24例(24·5%),*4/*4者1例(1·0%),根据基因型分为A组(CYP2A6*1/*1)和B组(CYP2A6*1/*4或CYP2A6*4/*4)。B组患者丙戊酸钠的标准血药浓度平均值(4·1393±0·2793)较A组(3·3486±0·3919)高,差异有统计学意义(P<0·05)。结论CYP2A6基因多态性影响丙戊酸钠的血药浓度,含有CYP2A6*4等位基因的患者应用丙戊酸钠应较常规降低用量。

Objective To investigate the effect of cytochrome P450 2A6 （CYP2A6） genetic polymorphisms on serum concentration of sodium valproate, Methods A total of 98 epileptic patients receiving sodium valproate after a period of more than 5 half-time were recruited. The genotypes of CYP2A6 of the patients were detected by nested-primer polymerase chain reaction （PCR） to examine the alleles CYP2A6 ＊ 1 and CYP2A6 ＊ 4. Fluorescence polarization immunoassay （FPIA） was used to measure the serum concentration of sodium valproate. Results Of the 98 cases, 73 （74. 5% ） were wild genotypes, 24 （24. 5% ） were CYP2A6 ＊ 1/＊ 4 genotypes and 1 （ 1.0% ） was CYP2A6 ＊ 4/＊ 4 genotype. According to the genotypes of CYP2A6 the patients were divided into two groups, one was group A （CYP2A6 ＊ 1/＊ 1 ） and the other was group B （CYP2A6 ＊ 1/＊ 4 or ＊ 4/＊ 4）. The mean value of the serum concentration of sodium valproate of the patients in group A（4. 1393 ±0. 2793） was higher than that in group B（3. 3486 ± 0. 3919 ） with a statistical significance （P 〈 0. 05 ）. Conclusions The genetic polymorphisms of CYP2A6 affect the serum concentration of sodium valproate. The dosage of sodium valproate in patients with CYP2A6 ＊ 4 allele should be lower than usual.