Brandl Eva J, Tiwari Arun K, Lett Tristram A, Shaikh Sajid A, Lieberman Jeffrey A, Meltzer Herbert Y, Kennedy James L, Müller Daniel J
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Hum Psychopharmacol. 2013 Mar;28(2):183-7. doi: 10.1002/hup.2288. Epub 2013 Jan 30.
Previous studies have shown that antipsychotics with high propensity for antipsychotic-induced weight gain (AIWG) influence glucose transporter type 4 (GLUT4) mediated glucose intake. Variation in the gene encoding TBC1 domain family member 1 (TBC1D1), a Rab-GTPase activating protein regulating GLUT4 trafficking, has been associated with obesity. Therefore, we investigated the impact of TBC1D1 polymorphisms on AIWG.
We analyzed rs9852 and rs35859249 in TBC1D1 in 195 schizophrenia subjects treated mostly with clozapine or olanzapine for up to 14 weeks. Association was tested using analysis of variance and analysis of covariance with change (%) from baseline weight as the dependent variable.
Analysis of covariance showed a non-significant trend for lower weight gain in carriers of the T-allele of rs9852 than in C-allele homozygotes (p = 0.063). This effect was more pronounced in the subgroup of patients treated with clozapine or olanzapine (p = 0.024). For rs35859249, no significant association with AIWG could be detected.
This is the first study examining the association between TBC1D1 and AIWG. The moderate association of rs9852, located in the 3'UTR near a miRNA binding site, indicates an influence of TBC1D1 on AIWG. Further investigations remain necessary to elucidate the role of this gene in AIWG.
先前的研究表明，具有较高致精神分裂症药物所致体重增加（AIWG）倾向的抗精神病药物会影响葡萄糖转运蛋白4（GLUT4）介导的葡萄糖摄取。编码TBC1结构域家族成员1（TBC1D1）的基因发生变异，TBC1D1是一种调节GLUT4转运的Rab-GTPase激活蛋白，与肥胖有关。因此，我们研究了TBC1D1基因多态性对AIWG的影响。
我们分析了195例主要使用氯氮平或奥氮平治疗长达14周的精神分裂症患者TBC1D1基因中的rs9852和rs35859249。使用方差分析和协方差分析进行关联性检验，以基线体重变化百分比作为因变量。
协方差分析显示，rs9852的T等位基因携带者的体重增加趋势低于C等位基因纯合子，但差异无统计学意义（p = 0.063）。在使用氯氮平或奥氮平治疗的患者亚组中，这种效应更为明显（p = 0.024）。对于rs35859249，未检测到与AIWG有显著关联。
这是第一项研究TBC1D1与AIWG之间关联的研究。位于3'UTR靠近miRNA结合位点的rs9852的中度关联表明TBC1D1对AIWG有影响。仍有必要进行进一步研究以阐明该基因在AIWG中的作用。
