Department of Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.
Int J Geriatr Psychiatry. 2013 Sep;28(9):925-32. doi: 10.1002/gps.3899. Epub 2012 Dec 20.
The primary aims of this study were to (i) determine whether folate metabolism genetic polymorphisms predict age of onset and occurrence of late life depression; and (ii) determine whether folate metabolism genetic polymorphisms predict response to antidepressant medications in late-life depression.
This study used the Conte Center for the Neuroscience of Depression and the Neurocognitive Outcomes of Depression in the Elderly Study database, which includes individuals aged ≥60. The folate nutrition assessment was determined by the Block Food Frequency Questionnaire. Genotype was evaluated for 15 single nucleotide polymorphisms from 10 folate metabolism genes. Logistic regression models were used to examine genetic polymorphisms and folate estimates with association with depression age of onset and remission status.
There were 304 Caucasians in the database, 106 of these were not depressed and 198 had a diagnosis of depression. There were no significant differences between remitters and non-remitters in age, sex or estimated folate intakes. There were no folate estimates or folate metabolism gene single nucleotide polymorphisms that significantly predicted age of onset of depression or occurrence of depression. Methionine synthase reductase (MTRR) A66G (rs1801394) was significantly associated with remission status (p = 0.0077) such that those with the AA genotype were 3.2 times as likely as those with the GG genotype to be in remission (p = 0.0020). Methylenetetrahydrofolate reductase A1298C (rs1801131) achieved a borderline significance for association with remission status (p = 0.0313).
The major finding from this study is that the MTRR A66G genotype predicts response to selective serotonin reuptake inhibitor antidepressants in late life depression.
本研究的主要目的是：(i)确定叶酸代谢基因多态性是否预测老年发病和晚年抑郁症的发生；(ii)确定叶酸代谢基因多态性是否预测老年抑郁症患者对抗抑郁药物的反应。
本研究使用了 Conte 中心的神经科学抑郁和老年抑郁的神经认知结果研究数据库，该数据库包含年龄≥60 岁的个体。叶酸营养评估通过 Block 食物频率问卷确定。10 个叶酸代谢基因中的 15 个单核苷酸多态性进行了基因分型评估。使用逻辑回归模型检查与抑郁发病年龄和缓解状态相关的遗传多态性和叶酸估计值。
数据库中有 304 名白种人，其中 106 名未患抑郁症，198 名患有抑郁症。缓解者和未缓解者在年龄、性别或估计叶酸摄入量方面无显著差异。没有叶酸估计值或叶酸代谢基因单核苷酸多态性可显著预测抑郁症的发病年龄或抑郁症的发生。甲硫氨酸合成酶还原酶（MTRR）A66G（rs1801394）与缓解状态显著相关（p=0.0077），即 AA 基因型的患者缓解的可能性是 GG 基因型的 3.2 倍（p=0.0020）。亚甲基四氢叶酸还原酶 A1298C（rs1801131）与缓解状态的相关性具有边缘意义（p=0.0313）。
本研究的主要发现是，MTRR A66G 基因型可预测选择性 5-羟色胺再摄取抑制剂抗抑郁药在老年抑郁症中的反应。
