MTHFR C677T 和 MS A2756G 多态性在重度抑郁症中的流行情况及其对氟西汀治疗反应的影响。
Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment.
机构信息
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA.
出版信息
CNS Spectr. 2012 Jun;17(2):76-86. doi: 10.1017/S1092852912000430.
OBJECTIVE
To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response.
METHODS
We screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20-60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined.
RESULTS
Prevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C = 41%, C/T = 47%, T/T = 11%, A/A = 66%, A/G = 29%, G/G = 4%). In the fluoxetine-treated subsample (n = 49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response.
CONCLUSION
The C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples.
目的
研究亚甲基四氢叶酸还原酶（MTHFR）基因 C677T 多态性和甲硫氨酸合成酶（MS）A2756G 多态性的流行情况及其对抗抑郁反应的影响。
方法
我们筛选了 224 名符合 SCID 诊断的重性抑郁障碍（MDD）患者（52%为女性，平均年龄 39±11 岁），并获得了 194 个基因样本。49 名患者（49%为女性，平均年龄 36±11 岁）参加了氟西汀 20-60mg/天的 12 周开放性临床试验。我们检测了临床反应与 C677T 和 A2756G 多态性、叶酸、B12 和同型半胱氨酸之间的关系。
结果
C677T 和 A2756G 多态性的发生率与以往报道一致（C/C=41%，C/T=47%，T/T=11%，A/A=66%，A/G=29%，G/G=4%）。在氟西汀治疗的亚组（n=49）中，C/C 患者的意向治疗（ITT）反应率为 47%，C/T 和 T/T 患者的 ITT 反应率为 46%（无显著性差异）。A/A 患者的 ITT 反应率为 38%，A/G 患者的 ITT 反应率为 60%（无显著性差异），没有 G/G 纯合子患者。A/G 患者的平均基线血浆 B12 明显低于 A/A 患者，但叶酸和同型半胱氨酸水平不受遗传状态的影响。血浆叶酸与治疗反应呈负相关。
结论
C677T 和 A2756G 多态性对抗抑郁反应无显著影响。这些初步发现需要在更大的样本中进行复制。
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