SLC1A1 基因变异与生活应激对强迫症药物抵抗的交互作用。
Interaction of SLC1A1 gene variants and life stress on pharmacological resistance in obsessive-compulsive disorder.
机构信息
1] Neuroscience Group-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), CIBERSAM (Centro de Investigación en Red de Salud Mental-Instituto de Salud Carlos III), L'Hospitalet de Llobregat, Barcelona, Spain [2] OCD Clinical and Research Unit, Department of Psychiatry, Bellvitge Hospital, Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona, Spain.
出版信息
Pharmacogenomics J. 2013 Oct;13(5):470-5. doi: 10.1038/tpj.2012.30. Epub 2012 Jul 10.
Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive-compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39-4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.
遗传和环境因素似乎相互作用并影响强迫症（OCD）的发病和病程，但谷氨酸转运体变体（SLC1A1）在药物抵抗中的作用尚不清楚。我们旨在评估 SLC1A1 中的遗传变异和发病时的生活应激是否相互作用并调节 OCD 中的药物抵抗。在 238 名 OCD 患者的样本中进行了 SLC1A1 基因组区域内的几个单核苷酸多态性的单标记关联研究。对于最强关联的 SNP（rs3087879），风险等位基因的一个拷贝增加了更高治疗抵抗的可能性（比值比=2.42；95%置信区间=1.39-4.21；P=0.0018），但仅在 OCD 患者发病时无生活应激的情况下。这些结果表明，在 OCD 中存在治疗抵抗的基因-环境相互作用效应，并增强了谷氨酸能系统在 OCD 现象学中的作用的现有证据。
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