CYP 2C19 與 CYP 2D6基因多型性之交互作用影響重度憂鬱症病人對Fluoxetine或 Venlafaxine早期治療反應

Interaction between CYP 2C19 and CYP 2D6 Genetic Polymorphisms Infl uences the Early Response of Fluoxetine/Venlafaxine Treatment among Patients with Major Depressive Disorder

目的：重度憂鬱症(major depressive disorder,MDD)病人的治療中，人類肝臟細胞色素P450(CytochromeP450)的基因多型性，CYP2C19*2G681A、CYP2C19*3G636A和CYP2D6*10C100T，對於fluoxetine及venlafaxine之治療反應的相關性至今仍尚未被釐清。在這個研究中，作者嘗試釐清以前的研究數據。方法：本研究納入140名重度憂鬱症的門診病人，以隨機分配的方式分組給予抗憂鬱劑fluoxetine或venlafaxine治療，並進行基因型的檢測。此外，於藥物治療前及治療後第二、第四、與第六週，使用21題版漢式憂鬱量表(21-itemHamiltonRatingScaleforDepression;HAM-D)對病人憂鬱症狀進行評估。結果：分析後發現，不論是CYP2C19*2G681A、CYP2C19*3G636A或CYP2D6*10C100T與fluoxetine及venlafaxine對於重度憂鬱症病人的治療反應未達顯著的相關。然而，進一步探討基因多型性變異間交互作用對於藥物治療反應之關係，發現對於venlafaxine治療組中，CYP2C19*2G681A和CYP2D6*10C100T的交互作用與第二週、第四週、第六週之療效具有相關性（p值分別為p<0.05、p<0.01和p<0.01）；另外於uoxetine治療組中發現，CYP2C19*3G636A和CYP2D6*10C100T的交互作用與第二週、第四週的療效有關（p值各別為p=0.001和p<0.05）。結論：CYP2C19兩個主要的基因多型性變異與CYP2D6基因之交互作用，對於uoxetine或venlafaxine的早期治療反應有顯著的關聯。

Objective:The relationship between CYP 2C19*2G681A, CYP 2C19*3 G636A and CYP 2D6*10C100T polymorphisms and the treatment response to fluoxetine or venlafaxine in patients with major depressive disorder (MDD) remains unclear. In this study, we intended to clarify this issue. Methods:One hundred and forty outpatients diagnosed with MDD were randomized into either the fluoxetine or venlafaxine treatment group and genotyped. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and biweekly over 6 weeks of treatment. Results:Neither polymorphisms of CYP 2C19*2G681A, CYP 2C19*3G636A nor that of CYP 2D6*10C100T genotype were associated with treatment response in either the fluoxetine or venlafaxine groups. When the effects of the SNP*SNP interaction on treatment response was examined, CYP 2C19*2G681A and CYP 2D6*10C100T had significant interactions effects on the treatment response at weeks 2, 4, and 6 (p< 0.05, p< 0.01 and p< 0.01, respectively) in the venlafaxine group, while CYP 2C19*3G636A and CYP 2D6*10C100T had significant interactions effects at weeks 2, and 4 (p= 0.001 and p< 0.05, respectively) in the fluoxetine group. Conclusion:The study results indicated that two major variants of CYP 2C19had significant interactions with CYP 2D6in the early response of fluoxetine/venlafax- ine treatment.