细胞色素P450酶2C19基因多态性对氟西汀治疗抑郁症患者疗效的影响

Effect of CYP2C19 gene polymorphism on fluoxetine antidepressant therapy

目的:探讨细胞色素P450酶2C19(CYP2C19)基因多态性对氟西汀治疗抑郁症患者疗效的影响。方法:连续招募152例抑郁症患者,采用DNA微阵列芯片法检测CYP2C19基因型。依据CYP2C19基因检测结果,将患者分为快代谢组、中等代谢组和慢代谢组,三组患者均单用氟西汀抗抑郁治疗,连续用药4周,记录三组治疗前后汉密尔顿抑郁量表17项(HAMD-17)评分及治疗过程中副反应量表(TESS)评分情况,以HAMD-17减分率≥50%定义为有效,二元logistic回归分析影响治疗效果的因素。结果:快代谢组、中代谢组和慢代谢组分别有58例(38.2%)、71例(46.7%)和23例(15.1%)患者。治疗前,三组HAMD-17评分差异无显著性;治疗后,慢代谢组HAMD-17评分显著低于快代谢组和中等代谢组(P<0.05);患者分组与治疗时间有交互作用(F=4.891,P=0.014),三组HAMD-17评分随治疗时间的变化趋势不同;慢代谢组治疗有效率显著高于快代谢组(P<0.05);治疗过程中,三组TESS评分差异无显著性;二元logistic回归分析显示,患者的病程(OR=0.576,P=0.012)是氟西汀抗抑郁治疗效果的独立影响因素,CYP2C19基因快代谢型患者应用氟西汀抗抑郁治疗有效的可能性是慢代谢型患者的22.6%(OR=0.226,P=0.009)。结论:CYP2C19慢代谢型患者应用氟西汀抗抑郁治疗疗效较好,CYP2C19基因多态性对氟西汀抗抑郁症治疗有影响。

Objective:To investigate the effect of cytochrome P450enzyme 2C19(CYP2C19)gene polymorphism on the efficacy of depressive patients treatment with fluoxetine.Methods:The CYP2C19genotype was detected by DNA microarray chip method in 152consecutive patients with depression.Based on the results of CYP2C19gene test,the patients were divided into fast metabolic group,moderate metabolic group and slow metabolic group.All three groups were treated with fluoxetine alone for 4weeks.The scores of 17items of Hamilton Depression Scale(HAMD-17)and the scores of side effects scale(TESS)were recorded before and after treatment.The reduction rate of HAMD-17≥50%was defined as effective,and binary logistic regression analysis was used to analyze the influencing factors of therapeutic effect.Results:The number and proportion of the fast metabolism group,the secondary metabolic group and the slow metabolism group were 58(38.2%),71(46.7%)and 23(15.1%),respectively.Before treatment,there was no significant difference in HAMD-17score among three groups;After treatment,the HAMD-17score of the slow metabolic group was significantly lower than that of the fast metabolic group and the moderate metabolic group(P<0.05).There was interaction between patients'groups and treatment time(F=4.891,P<0.05),and the change trend of HAMD-17score in three groups was different with the treatment time.The effective rate of the slow metabolic group was significantly higher than that of the fast metabolic group(P<0.05);During the treatment,there was no significant difference in TESS scores among three groups.Bivariate logistic regression analysis showed that the course of disease(OR=0.576,P<0.05)was an independent factor of the effect of fluoxetine on antidepressant,and the possibility of effective antidepressant treatment in the fast metabolism group was 22.6%of the slow metabolism group(OR=0.226,P<0.01).Conclusion:Antidepressant therapy with fluoxetine is more effective in CYP2C19patients with slow metabolism,and CYP2C19gene polymorphism has influence on fluoxetine antidepressant therapy.