神经源型一氧化氮合酶C276T基因多态性与抗抑郁疗效相关分析

目的探讨抑郁症患者血浆一氧化氮（NO）水平及神经源型一氧化氮合酶（nNOS）基因C276T多态性与抗抑郁剂疗效相关性。方法抑郁症患者予选择性5-羟色胺再摄取抑制剂（SSRIs）单药治疗8周,采用汉密尔顿抑郁量表（HAMD）评估患者抑郁症状严重程度;采用硝酸盐还原酶法测定正常对照组及抑郁症患者治疗前后血浆NO水平;全部受试者提取基因组DNA,并采用PCR-RFLP方法对nNOS基因C276T多态性进行基因分型。结果患者组疗前血浆NO水平为（76.8±31.6）μmol/L,显著高于疗后[（66.9±25.7）μmol/L,P=0.044]及正常对照组[（64.2±33.3）μmol/L,P=0.02],患者组疗后血浆NO水平为（66.9±25.7）μmol/L,与正常对照组（64.2±33.3）μmol/L相比差异无显著性（P=0.588）;患者组疗前HAMD评分为（24.3±4.3）分,疗后HAMD评分为（10.5±5.0）分,治疗前后HAMD减分率为（57.5±15.9）%;疗前血浆NO水平为（76.8±31.6）μmol/L,与疗前HAMD评分（24.3±4.3）分显著正相关（r=0.311,P=0.009）;nNOS基因可见两种等位基因条带C、T,组成三种基因型CC、CT、TT,携带不同基因型患者治疗前后HAMD评分和HAMD减分率差异无显著性（P〉0.05）。结论血浆NO浓度可能提示抑郁症急性发作期病情严重程度;nNOS基因C276T多态性可能不是影响抗抑郁剂治疗疗效的主要遗传因素。

Study of the association between neuronal nitric oxide synthase gene polymorphism and antidepressant effect in depressed patients

Objective To investigate whether there is an association between plasma nitric oxide（NO）concentrations or neuronal nitric oxide synthase（nNOS）gene C276T polymorphism and antidepressant effect in depressed patients.Methods Plasma NO concentrations were measured in depressed patients before and after 8-weeks SSRIs antidepressant treatment and normal controls by spectrophotometer.The 17-item Hamilton Depression Rating Scale（HAMD）was used to evaluate clinical depression symptom.The HAMD reduction ratio was used to evaluate the antidepressant effect.Genotyping was performed using PCR-RFLP techniques both in patients and normal controls.Results The plasma NO concentrations in acute episode untreated depressed patients（76.8±31.6）μmol/L were significantly higher than that in the patients after 8-weeks antidepressant treatment [（66.9±25.7）μmol/L,P=0.044]and normal controls[（64.2±33.3）μmol/L,P=0.02].There was no significant difference between the plasma NO concentrations in treated patients and normal controls（P=0.588）.The plasma NO concentrations in untreated patients were significantly positively associated with baseline HAMD scores（24.3±4.3）（r=0.311,P=0.009）.Genotypes of nNOS were not associated with HAMD scores（P0.05）.Conclusion These data provide a possibility that plasma NO concentrations are likely to be indicator for severity of the clinical symptoms in depressend patients.The nNOS gene C276T polymorphism are unlikely to play important roles on antidepressant effect.