儿茶酚氧位甲基转移酶基因功能多态性对帕罗西汀治疗2型糖尿病伴抑郁患者疗效的相关性

Relationship between polymorphism of COMT gene and clinical outcomes of depression in patients with type 2 diabetes treated with paroxetine

目的:探讨儿茶酚氧位甲基转移酶(COMT)基因功能多态性对帕罗西汀治疗2型糖尿病合并抑郁焦虑患者的疗效的影响。方法:对52例血糖控制不理想的2型糖尿病合并抑郁焦虑患者,治疗前抽取外周静脉血,提取DNA,用PCI技术检测研究对象的基因型,分成Val/Val、Val/Met和Met/Met 3组,在常规降糖治疗基础上加用帕罗西汀每晨一次,每次20 mg,疗程4周,观察治疗前、后汉密尔顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)分数、餐后2 h血糖(2hPBG)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、帕罗西汀血药浓度的改变。结果:治疗后不同基因组患者抑郁情绪有改善,HAMD、HAMA、2hPBG、FBG、HbA1c、血药浓度与治疗前比较均有显著性差异(P<0.01),但4周后3基因组间差异并无显著性(P>0.05)。结论:对2型糖尿病合并抑郁焦虑患者,加用帕罗西汀治疗能有效改善抑郁症状及更好地控制血糖,COMT基因功能多态性与帕罗西汀疗效差异可能并不相关。

OBJECTIVE To investigate the relationship between the polymorphism of COMT gene and clinical outcomes of depression in patients with type 2 diabetes treated with paroxetine. METHODS Fifty-two type 2 diabetes mellitus patients accompanied with depression were treated with paroxetine（20 mg,qd） for 4 weeks. DNAs of peripheral blood leukocytes from 52 patients with type 2 diabetes were obtained before therapy and were analyzed for genotypes by PCR-RFLP method. They were divided into three groups of Val/Val, Val/Met and Met/Met. Hamilton depression scale （HAMD）, Hamilton anxiety scale （HAMA）. 2hPGB, FBG, HbA1c levels and plasma concentration were obtained to monitor glycemie control. RESULTS Paroxetine significantly improved the symptoms of depression and anxiety in type 2 diabetes mellitus with depression. At the end of the 4th week, the levels of 2hPBG, FBG, HbA1c and scores of both the HAMD and HANA decreased compared with pre-treat ment （P〈0. 01 ）. But comparison among groups were undifferentiated （P〈0. 05）. CONCLUSION Paroxetine effectively reduce the severity of depression in diabetic patients. It was also suggested that the polymorphism of COMT gene doesn＇t associate with the therapeutic efficacy variance of paroxetine in type 2 diabetes mellitus patients accompaied with depression.