5-羟色胺和去甲肾上腺素转运体基因多态性的交互作用与重性抑郁障碍临床疗效的关联研究  

The association study between the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors

作　　者：孟亚琴[1,2] 孙宁[1,2] 王彦芳[1,2] 段慧君 李素萍[1,2] 彭菊意 杜巧荣[1,2] 张克让 

机构地区：[1]山西医科大学心理卫生研究所,太原030001 [2]山西医科大学第一医院

出　　处：《中华行为医学与脑科学杂志》2013年第3期212-214,共3页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金面上项目（30971054,81171290）;山西省科技攻关项目（2007031091-3）;山西省青年科技研究基金项目（2011021036-1）

摘　　要：目的探讨5-羟色胺和去甲肾上腺素转运体基因多态性的交互作用与选择性5-羟色胺再摄取抑制剂临床疗效的关联研究。方法收集符合美国精神障碍诊断与统计手册第四版（DSM—IV）重性抑郁障碍（MDD）诊断标准的患者246例，给予选择性5-羟色胺再摄取抑制剂（SSRIs）西酞普兰（20～60mg／d）或帕罗西汀（20～60mg／d），在治疗后1，2，4，6周运用17项汉密尔顿抑郁量表（HAMD）评定临床疗效；应用聚合酶链反应技术（PCR）、聚丙烯酰胺凝胶电泳（SDS—PAGE）及DNA直接测序检测5-羟色胺转运体（5-HTT）基因多态性VNTR、LPR和去甲肾上腺素转运体（NET）基因多态性rs2242446、rs5569；采用SPSSl3．0软件进行统计分析。结果（1）治疗6周末时，5-H．rrLPR基因多态性SSRIs疗效有关（P=0．023），即LL基因型比SS＋LS基因型有效率高（OR值=2．225，OR95％CI=1．118，4．427）；（2）5-HTT LPR和NET rs5569交H作用与SSRIs疗效有统计学意义（P=0．01）。结论研究发现5-HTT LPR和NET rs5569交互作川可能与中国汉族MDD患者SSRIs抗抑郁药物疗效有关。Objective To explore the relevance of the interaction of serotonin and norepinephrine transporter gene polymorphisms and the effects of selective serotonin reuptake inhibitors. Methods The subjects comprised 246 patients according to the diagnostic and statistical manual of mental disorders in the fourth edition （DSM-IV） criterion for major depressive disorder（MDD）. The clinical efficacy were assessed by using 17 Hamilton depression quantity （HAMD） scale after selective serotonin reuptake inhibitors（SSRIs） citalopram （20 to 60 mg/d ） or paroxetine （ 20 to 60 rag/d） were used randomly for 1,2,4,6 weeks. Polymerase chain reaction （ PCR）, sodium dodecyl sulfate polyacrylamide gel electrophoresis（ SDS-PAGE ）and DNA sequencing analysis were used to detect the genntype of 5-HTF gene single nucleotide polymorphisms （SNP） of VNTR and LPR and SNPs at rs2242446 and rs5569 of NET. SPSSI 3.0 software were used for statistical analysis. Results （ 1 ） An association between 5-HTT LPR and the efficacy of SSRIs was found after 6 weeks in these samples （P = 0. 023 ）. The clinical efficiency of LL genotype was higher than SS ＋ LS genotype（ OR = 2. 225, OR 95% CI= 1.118,4.427 ）. （2） The interaction of 5-HTT LPR and NET rs5569 and the SSRIs antidepressant effects was statistical significance （P = 0.01 ）. Conclusion Preliminary study found that the interaction of 5-HTT LPR and NET rs5569 may be related to SSRIs antidepressant effects in China＇ s patients with MDD.

关 键 词：重性抑郁障碍 5-羟色胺转运体 去甲肾上腺素转运体 基因多态性 交互作用 

分 类 号：R749.4[医药卫生—神经病学与精神病学]