抑郁症患者多药耐药基因多态性对度洛西汀稳态血药浓度和临床疗效的影响

摘要

Objective To explore the potential influence of MDR1 gene polymorphisms, induding exon 26 C3435T and exon 21 G2677T, on the blood concentration and therapeutic effects of duloxetine in patients with depression.Methods The diagnosis of depression was made based on the Chinese Classification and Diagnosis of Mental Diseases-3rd edition. One hundred twenty depressed patients were received duloxetine treatment for 8 weeks. The patients were assessed and rated by 24-item Hamilton depression rating scale before and after the treatment, and the blood drug levels were assayed at 8th week. MDR1 variants G2677T and C3435T were detected using RFLP. Results After 8 week treatment, there were statistical significances in the steady blood concentration and therapeutic response to duloxetine in patients with different MDR1 variants G2677T (P ＜ 0. 05), and patients with TT genotype had higher concentration of duloxetine compared with patients with GC or GG genotype[( 34. 22 ± 2. 41 ) ng/mL, ( 31.49 ± 3.32 ) ng/mL, ( 32. 40 ± 2. 89 ) ng/mL, P ＜ 0. 05 )and had better therapeutical outcomes than patients with GG genotype (mean rank70. 38 vs 51.65, P ＜ 0. 05 ). There were statistical significances in the steady blood concentration and therapeutic response to duloxetine in patients with different C3435T variants ( F = 6.93, P ＜ 0. 01; x2 =6. 36, P =0. 04). Patients with TT genotype had higher concentration of dulo xetine compared with patients with CC or CT genotype [ (33. 99 ± 2. 40) ng/mL, (31.53 ± 3. 41 ) ng/mL, (32. 32 ±2. 96) ng/mL, P ＜ 0. 05 ] and had better therapeutical outcomes than patients with CC genotype (mean rank 69. 11 vs 51.16, P ＜0. 05). Conclusions MDR1 gene polymorphisms are associated with the steady blood concentration and the anti-depression effects of duloxetine.%目的 探讨抑郁症患者多药耐药1(multidrug resistance 1, MDR1)基因的G2677T和C3435T位点多态性对度洛西汀稳态血药浓度和临床疗效的影响.方法 120例符合中国精神障碍分类与诊断标准第3版(CCMD-3)抑郁发作标准的抑郁症患者接受度洛西汀治疗8周.在治疗前后采用汉密尔顿抑郁量表评估患者病情,检测8周时度洛西汀稳态血药浓度.检测患者的MDR1基因的G2677T/C3435T多态性.结果 8周后,MDR1基因的G2677T位点的不同基因型患者组之间度洛西汀稳态血药浓度和疗效的差异均有统计学意义(P＜0.05),TT基因型组的度洛西汀稳态血药浓度高于GG 和GT基因型组[(34.22±2.41)ng/mL,(31.49±3.32)ng/mL,(32.40±2.89)ng/mL, P＜0.05],TT型患者组的疗效评分平均秩次较GG型患者组高(70.38 vs 51.65, P＜0.05);C3435T位点的不同基因型患者组之间的度洛西汀稳态血药浓度和疗效差异有统计学意义(P＜0.05),TT型的度洛西汀稳态血药浓度较CC型和CT型高[ (33.99±2.40) ng/mL, (31.53±3.41) ng/mL, (32.32±2.96) ng/mL, P＜0.05],TT基因型患者组的疗效平均秩次优于CC基因型组(69.11 vs 51.16, P＜0.05).结论 MDR1基因G2677T/C3435T多态性与度洛西汀稳态血药浓度和疗效可能有关.