The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study
The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study
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DOI：
10.1016/j.jad.2010.08.009
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发表时间：
2011-03-01
影响因子：
6.6
通讯作者：
Lavebratt, Catharina
中科院分区：
文献类型：
--
作者：
Aberg, Elin;Fandino-Losada, Andres;Lavebratt, Catharina
背景资料：环境风险因素与遗传脆弱性一起创造了一个复杂的背景，以发展depression.Methods：我们调查了之间的关联COMT瓦尔（158）Met和抑郁症在瑞典人口为基础的样本405抑郁症患者（抑郁症诊断，心境恶劣或混合焦虑抑郁症定义根据DSM-IV）和2,151健康对照。我们还分析了这种遗传变异与抑郁症的一些环境危险因素之间的相互作用，以及这种多态性与抑郁症个体中发现的低动机水平和消极情绪状态之间的联系。抑郁症患者Met/Met和Met/瓦尔基因型频率高于对照组（OR = 1.49，CI 95%= 1.11-2.00，P = 0.009）。仅在男性中发现相关性（OR = 2.26，CI 95%= 1.26-4.05，p = 0.008）。回归分析包括一些潜在的抑郁症的危险因素，进一步表明，Met/Met和Met/瓦尔与男性抑郁症（P = 0.005）。基因型与家庭儿童问题之间存在交互作用（RERI = 0.876，CI 95%= 0.090-1.662和AP = 0.426，CI 95%= 0.030-0.821）。此外，Val等位基因纯合子的抑郁症男性比Met变异的抑郁症男性有更高的动机水平（P = 0.02）。局限性：当根据性别和基因型对病例进行分层时，每组抑郁个体的样本量被认为是一个局限性。COMT瓦尔（158）Met的Met变异体是抑郁症和低动机水平的风险变异体，但不是女性。具有这种风险变体的个体与有问题的童年相结合，患抑郁症的风险更高。(C)2010爱思唯尔有限公司版权所有。
Background: Environmental risk factors together with genetic vulnerability create a complex background to develop depression.Methods: We investigated the associations between COMT Val(158)Met and depression in a Swedish population-based sample of 405 depressed individuals (major depression diagnosis, dysthymia or mixed anxiety depression defined according to DSM-IV) and 2,151 healthy controls. We also analyzed interaction between this genetic variation and some environmental risk factors for depression and the link between this polymorphism and the low motivational level and negative mood state found in depressed individuals.Results: Depressed individuals displayed a higher frequency of the Met/Met and Met/Val genotypes compared to controls (OR = 1.49, CI95% = 1.11-2.00, P = 0.009). The association was found among men only (OR = 2.26, CI95% = 1.26-4.05, p = 0.008). Regression analysis including some potential risk factors for depression, did further indicate that Met/Met and Met/Val were associated with depression in men (P = 0.005). There was also an interaction between genotype and family childhood problems (RERI = 0.876, CI95% = 0.090-1.662 and AP = 0.426, CI95% = 0.030-0.821). Further, depressed men homozygous for the Val-allele, had a higher motivational level than depressed men with a Met-variant (P = 0.02).Limitations: The sample size of depressed individuals per group when stratifying cases according to gender and genotypes is considered a limitation.Conclusions: The Met-variants of COMT Val(158)Met are risk variants for depression and low motivational level in depressed Swedish men, but not women. Individuals with this risk variant in combination with a problematic childhood, have an even higher risk to develop depression. (C) 2010 Elsevier B.V. All rights reserved.