De Luca Vincenzo, Mueller Daniel J, de Bartolomeis Andrea, Kennedy James L
University of Toronto, Centre for Addiction and Mental Health, Neurogenetics Section, Toronto, ON, Canada.
Int J Neuropsychopharmacol. 2007 Oct;10(5):697-704. doi: 10.1017/S1461145707007547. Epub 2007 Feb 12.
The 5-HT2C receptor has been hypothesized to represent an important modulator in feeding behaviour. Evidence was based on the observation that knock-out mice for the 5-HT2C receptor gene (HTR2C) develop obesity and that many atypical antipsychotics with potent 5-HT2C antagonism may induce weight gain in susceptible individuals. Pharmacogenetic studies focusing mainly on the -759C/T promoter polymorphism (rs3813929) of the X-linked HTR2C gene revealed controversial results. We investigated the association of the HTR2C gene and weight gain using meta-analytical techniques, combining all published data while restricting our analysis to studies investigating the 759C/T. We also investigated whether ancestry (Caucasian vs. Asian) and clinical factors moderated any association. We found evidence for a slight association of -759C/T with weight gain and significance between studies for heterogeneity. Our meta-analysis provides support for the association of HTR2C in weight gain but indicates that firmly establishing the role of pharmacogenetics in clinical psychiatry requires much larger sample sizes that have been hitherto reported.
5-羟色胺2C受体（5-HT2C受体）被认为是进食行为中的一种重要调节因子。证据基于以下观察结果：5-HT2C受体基因（HTR2C）敲除小鼠会出现肥胖，并且许多具有强效5-HT2C拮抗作用的非典型抗精神病药物可能会使易感个体体重增加。主要针对X连锁HTR2C基因的-759C/T启动子多态性（rs3813929）的药物遗传学研究得出了有争议的结果。我们使用荟萃分析技术研究了HTR2C基因与体重增加之间的关联，汇总了所有已发表的数据，同时将分析限制在研究-759C/T的研究中。我们还研究了血统（白种人与亚洲人）和临床因素是否会调节任何关联。我们发现了-759C/T与体重增加之间存在轻微关联的证据，以及研究之间存在异质性的显著性。我们的荟萃分析为HTR2C在体重增加中的关联提供了支持，但表明要在临床精神病学中牢固确立药物遗传学的作用，需要比迄今报道的大得多的样本量。
