中国汉族癫患者CYP3A5*3基因多态性与卡马西平药物浓度的相关性研究

Effect of CYP3A5*3 Genotype on Serum Carbamazepine Concentrations at Steady-state in Han Chinese Epileptic Patients

目的:观察CYP3A5*3基因多态性与中国汉族癫患者卡马西平稳态药物浓度的相关性。方法:检测采用177例卡马西平单药治疗的中国汉族癫患者的稳态药物浓度,LDR-PCR测序分型检测CYP3A5*3基因多态性。结果:CYP3A5*3基因AA型的卡马西平标准化浓度为(0.23±0.066)μg.mL-1,AG型为(0.24±0.053)μg.mL-1,GG型为(0.31±0.073)μg.mL-1。3种基因型间标准化血药浓度差异有统计学意义(P<0.000 1),且AA型低于GG型(P<0.000 1),AG型低于GG型(P<0.000 1),差异均有统计学意义。AA型虽有低于AG型趋势,但差异无统计学意义(P=0.087)。CYP3A5*3各基因型间血药浓度、剂量校正浓度间差异与上述结果类似。结论:CYP3A5*3基因型影响中国汉族癫患者的卡马西平药物浓度,是造成卡马西平药物浓度个体差异的可能因素。

Aim： To assess the effect of CYP3A5＊3 genotype on serum carbamazepine （CBZ） concentrations at steady-state. Methods： The serum concentrations of CBZ in 177 Han Chinese epileptic patients with CBZ- monotherapy and their CYP3A5＊3 genotype were determined by LDR-PCR method. Results： The normalized concentrations of CBZ were （0.23± 0.066） μg·mL-1 for CYP3A5＊3 AA allele, （0.24 ±0.053）μg·mL-1 for AG allele and （0.31 ± 0.073） μg·mL-1 for GG allele in 177 Han Chinese epileptic patients. There were significant differences among these three genotypes （P〈0.000 1）. The normalized concentrations of CBZ were significant higher in GG allele. But there was no significant difference between AA allele and AG allele. The same result was found in non-normalized concentrations. Conclusion： The CYP3A5＊3 genotype affected the CBZ concentrations in Han Chinese patients that the normalized concentrations of CBZ in patients of GG allele were higher. And it may be a factor that contributes to individual variability in CBZ disposition in Han Chinese epileptic patients.