重性抑郁障碍患者多药耐药基因多态性与帕罗西汀疗效及不良反应的关联研究

Association study of multidrug resistance 1 gene polymorphisms with efficacy and adverse drug reaction of paroxetine in major depressive patients

目的探索中国汉族重性抑郁障碍（MDD）患者多药耐药基因（MDR1）多态性与帕罗西汀疗效及药物不良反应的关联。方法对116例MDD患者给予帕罗西汀治疗，剂量范围20-50mg／d，疗程8周。采用限制性片段长度多态性技术及DNA测序方法检测MDRl基因上5个单核苷酸多态性的基因型，分析各位点基因型及多位点组成的单体型与帕罗西汀临床效应的关系。结果携带rs1128503位点CC基因型患者的临床缓解率低于其他基因型携带者（TT基因型86．0％，CT基因型72．4％，CC基因型50．0％，P〈0．05），且焦虑／躯体化因子减分率较低（P〈0．05）。携带单体型C．A（rs1128503-rs1202169）患者的临床痊愈率（69．7％）低于非携带者（86．0％），P〈0．05。而携带单体型T-A／T-T-G（rs1045642-rs2032582-rs1128503-rs1202169）的患者药物不良反应发生率（29．0％）低于非携带者（49．0％），P〈0．05。结论MDR1基因多态性可能与中国汉族MDD患者帕罗西汀的疗效及不良反应关联。

Objective To explore the muhidrug resistance 1 （MDR1） polymorphisms with the therapeutic efficacy and adverse drug reaction （ADR） of paroxetine in Chinese Han major depressive disorder （MDD） patients. Methods Polymerase chain reaction-restriction fragment length polymorphism or DNA sequencing were used to genotype 5 single nucleotide polymorphisms of MDR1 gene in 116 MDD patients treated with 20-50 mg/d paroxetine for 8 weeks. Association of the 5 SNPs and haplotypes with the clinical response to paroxetine was analyzed. Results The MDD patients with genotype CC of rs1128503 were associated with lower rates of remission （ TT 86. 0%, CT 72.4%, CC 50. 0%, P 〈 0. 05 ） and with lower reducing score rates of anxiety/somatization factor （P 〈 0. 05 ）. Patients with the haplotype C-A （rs1128503-rs1202169） showed lower remission rates （ C-A 69. 7% vs. Non-C-A 86. 0% , P 〈0. 05）, and patients with the haplotype T-A/T-T- G （rs1045642-rs2032582-rs1128503-rs1202169 ） exhibited lower rates of ADR （ T-A/T-T-G 29. 0% vs. Non-T-A/T-T-G 49. 0%, P 〈 0. 05 ）. Conclusion Among Han Chinese, the polymorphisms of the MDRI gene may be associated with the efficacy and adverse drug reaction of paroxetine in MDD patients.