Pouget Jennie G, Gonçalves Vanessa F, Nurmi Erika L, P Laughlin Christopher, Mallya Karyn S, McCracken James T, Aman Michael G, McDougle Christopher J, Scahill Lawrence, Misener Virginia L, Tiwari Arun K, Zai Clement C, Brandl Eva J, Felsky Daniel, Leung Amy Q, Lieberman Jeffrey A, Meltzer Herbert Y, Potkin Steven G, Niedling Charlotte, Steimer Werner, Leucht Stefan, Knight Jo, Müller Daniel J, Kennedy James L
• Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Toronto, ON, Canada.
Pharmacogenomics. 2015 Jan;16(1):5-22. doi: 10.2217/pgs.14.158.
TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain.
PATIENTS & METHODS: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119).
TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10(-3)), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10(-3)) and RUPP samples (p = 2.76 × 10(-4)).
Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect.
转运蛋白18 kDa（TSPO）是一种神经炎症生物标志物，也是精神疾病中新兴的治疗靶点。我们评估了TSPO基因多态性是否导致精神分裂症个体间差异、抗精神病药物疗效及抗精神病药物所致体重增加。
我们分析了670例精神分裂症患者和775名健康对照者的TSPO基因多态性。探讨了TSPO与其他线粒体膜蛋白编码基因（电压依赖性阴离子通道1（VDAC1）和腺嘌呤核苷酸转运体1（ANT1））之间的基因-基因相互作用。在两个独立样本（慕尼黑，n = 300；卢旺达大学项目（RUPP），n = 119）中对阳性结果进行了评估。
在发现样本（Puncor = 0.04）和RUPP样本（p = 3.00×10−3）中，TSPO rs6971与抗精神病药物所致体重增加独立相关，且在发现样本（p = 1.15×10−3）和RUPP样本（p = 2.76×10−4）中与ANT1 rs10024068存在相互作用。
我们的研究结果突出了TSPO作为未来抗精神病药物所致体重增加研究的候选因素，并支持线粒体膜成分参与这一严重治疗副作用。
