A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity
A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity
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DOI：
10.1007/s00213-010-1915-7
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发表时间：
2011-03-01
影响因子：
3.4
通讯作者：
Harro, Jaanus
中科院分区：
文献类型：
--
作者：
Reif, Andreas;Kiive, Evelyn;Harro, Jaanus
神经元型一氧化氮合酶（NOS 1）基因敲除导致小鼠在不利的住房条件下的冲动性攻击增加。与此相一致，我们以前已经表明，NOS 1的功能启动子多态性，称为NOS 1 ex 1f-VNTR，与冲动相关的性状和相关disorders.This研究的目的是研究是否不利的环境与冲动相关的措施的风险等位基因相互作用。我们在这里研究了一个以人口为基础的队列爱沙尼亚小学生，招募在9岁的年龄，并随访了9年。对于435名受试者，测量冲动性（适应性和适应不良冲动量表，BIS-11，停止信号数据和视觉比较测试，VCT），环境条件我们发现基因型主效应，即短NOS 1 ex 1f-VNTR等位基因的存在与较高水平的适应性冲动相关，尤其是在男性中，而且在VCT和停止信号测试中表现更差。应激性生活事件和不良家庭环境均与危险基因型交互作用，增加了适应不良的冲动行为，本研究进一步证明了NOS 1 ex 1f-VNTR短等位基因与冲动行为有沿着关系。在没有不利的环境条件下，这可能会导致有益的影响，因为冲动的功能形式受到影响。然而，在消极的条件下，这是相反的，因为在这些情况下，功能失调的冲动会增加。这些数据提供了证据表明，NOS 1 ex 1f-VNTR是受平衡选择可能解释的风险等位基因在人群中的持久性。
Neuronal nitric oxide synthase (NOS1) knockout results in increased impulsive aggression in mice under adverse housing conditions. In line with this, we have previously shown that a functional promoter polymorphism of NOS1, termed NOS1 ex1f-VNTR, is associated with impulsivity-related traits and related disorders.This study aims to examine whether adverse environment interacts with the risk allele on impulsivity-related measures.We here studied a population-based cohort of Estonian pupils, recruited at the age of 9 years and followed up for another 9 years. For 435 subjects, measures on impulsivity (Adaptive and Maladaptive Impulsivity Scale, BIS-11, Stop Signal data, and Visual Comparison Test, VCT), environmental conditions (stressful life events and family environment), and NOS1 ex1f-VNTR genotype were available.We found a genotype main effect in that presence of a short NOS1 ex1f-VNTR allele was associated with higher levels of adaptive impulsivity, especially in males, but also worse performance in the VCT and the Stop Signal test. Both stressful life events as well as adverse family environment interacted with the risk genotype to increase maladaptive impulsivity.This study provides further evidence that short alleles of NOS1 ex1f-VNTR go along with impulsive behavior. In the absence of adverse environmental conditions, this may lead to a beneficial effect as functional forms of impulsivity are affected. This however is reversed under negative conditions, as dysfunctional impulsivity is increased under these circumstances. This data provides evidence that NOS1 ex1f-VNTR is subject to balancing selection potentially explaining persistence of the risk allele in the population.