5-羟色胺转运蛋白基因多态性与抗抑郁药临床疗效的关系

目的:研究南京地区人群中5-羟色胺转运蛋白(5-HTT)基因多态性与血浆5-羟色胺(5-HT)浓度及选择性5-羟色胺再摄取抑制剂(SSRIs)的抗抑郁临床疗效是否存在相关性。方法;采用聚合酶链式反应(PCR)多态性分析技术对132例抑郁症患者和100名健康者进行基因型分析;HPLC-ECD法分析血浆中5-HT浓度;用汉密尔顿抑郁量表(HAMD)评定抗抑郁药的疗效。结果:抑郁症5-HTT基因基因型频率(LL24.2％,LS44.7％,SS31.1％)、等位基因频率(L46.59％,S53.41％);与正常对照组基因型频率(LL29.0％,LS47.0％,SS24.0％)、等位基因频率(L52.5％,S47.5％)比较无显著性差异(P>0.05);不同基因型抑郁症患者治疗前HAMD总分有显著差异,F=6.48,P=0.0021:经4wk SSRIs类抗抑郁药治疗后,HAMD总分均显著下降,减分值有显著差异,F=3.38,P=0.037;治疗前不同基因型患者5-HT浓度有显著差异,F=5.38,P=0.005 7;4wk治疗后,血浆中5-HT浓度均升高,不同基因型的增高值有明显差异,F=23.55,P<0.01。结论:南京地区人群中5-HTT基因多态性与抑郁症的发病不存在相关性,但与抑郁症疾病严重程度和SSRIs治疗效应存在显著的相关性,这一区域的基因型可能成为抑郁症患者实现个体化治疗的一个参考指标。

Relationship of clinical response between 5-HTT gene polymorphism and plasma 5-HT lever

AIM: To investigate the relationship between 5-hydroxytryptamine transporter (5-HTT) gene polymorphism and plasma 5-hydroxytryptamine (5-HT) lever, clinical response of selective serotonin reuptacke inhibitors (SS-RIs) in Chinese depressive patients. METHODS: Polymerase chain reaction (PCR) was used to detect the polymorphism of 5-HTT gene in 132 depressive patients and 100 controls. HPLC-electrical chemistry detector method was used to analyse plasma 5-HT lever. The depressive states were assessed with Hamilton Depression Rating Scale (HAMD). RESULTS: There were no significant differences of the 5-HTT polymorphism genotypes and alleles between 132 depressive patients (LL24.2%, LS44.7%, 3531.1%; L46.59%, 853.41%) and 100 controls (LL29.0%, 1547.0%, SS 24.0% ; L 52.5 % , S 47.5%), P > 0.05. The HAMD and plasma 5-HT lever of pre-treatment were significant differences in depressive patients with different 5-HTT genotype (F = 6.48, P = 0.002 1; F = 5.38, P =0.005 7). The HAMD reductive date and plasma 5-HT lever increasing date of 4 wk SSRIs post treatment were significant differences in depressive patients with different 5-HTT genotype ( F = 3.38, P < 0.01; F = 23.55, P < 0.01). CONCLUSION: The 5-HTT polymorphism is not associated with depression, but is associated with disease serious degree and SSRIs clini- cal responses in Chinese.