MCHR2和MCHR2-AS1基因多态性对精神病患者及现患或曾患非典型抑郁症的人群体重指数的影响。
Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression.
作者信息
Delacrétaz Aurélie, Preisig Martin, Vandenberghe Frederik, Saigi Morgui Nuria, Quteineh Lina, Choong Eva, Gholam-Rezaee Mehdi, Kutalik Zoltan, Magistretti Pierre, Aubry Jean-Michel, von Gunten Armin, Castelao Enrique, Vollenweider Peter, Waeber Gerard, Conus Philippe, Eap Chin B
机构信息
Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
出版信息
PLoS One. 2015 Oct 13;10(10):e0139155. doi: 10.1371/journal.pone.0139155. eCollection 2015.
Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.
精神药物治疗期间肥胖的发展是精神病学中的一个主要健康问题。黑色素浓缩激素受体2（MCHR2）是参与能量稳态的核心受体。MCHR2与其启动子区域与MCHR2-AS1共享，MCHR2-AS1是一种长链反义非编码RNA。本研究的目的是确定MCHR2和MCHR2-AS1的标签单核苷酸多态性（tSNP）是否与精神病患者和普通人群的体重指数（BMI）相关。首先在一个发现性精神病样本（n1 = 474）中研究了MCHR2和MCHR2-AS1 tSNP对BMI的影响。在另外两个精神病样本（n2 = 164，n3 = 178）和两个基于人群的样本（CoLaus，n4 = 5409；GIANT，n5 = 113809）中对阳性结果进行了重复验证。在发现性样本中，rs7754794C>T的TT携带者的BMI比C等位基因携带者低1.08 kg/m2（p = 0.04）。这一观察结果在一个独立的精神病样本中得到了重复验证（-2.18 kg/m2；p = 0.009）。rs7754794C>T与BMI之间的关联在年龄小于45岁（年龄中位数）的受试者中似乎更强。在基于人群的样本中，在较年轻个体（<45岁）中观察到中度关联（-0.17 kg/m2；p = 0.02）。有趣的是，这种关联完全由符合非典型抑郁症终生标准的患者驱动，即主要抑郁发作伴有食欲增加等症状。事实上，携带rs7754794-TT的非典型抑郁症患者的BMI值比C等位基因携带者低1.17 kg/m2（p = 0.04），在较年轻个体中这种效应更强（-2.50 kg/m2；p = 0.03；rs7754794与年龄之间的相互作用：p值 = 0.08）。这项研究为MCHR2和/或MCHR2-AS1对精神病患者肥胖的可能影响以及非典型抑郁症的病理生理学提供了新的见解。
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