Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia.
School of Nursing, Universidad de Ciencias Aplicadas y Ambientales UDCA, Bogotá, Colombia.
Eur Psychiatry. 2015 Jun;30(4):499-503. doi: 10.1016/j.eurpsy.2015.03.002. Epub 2015 Apr 1.
Interpersonal violence and suicide are among the main causes of mortality and morbidity around the world. In several developing countries, such as Colombia, they are among the first five entities of public health concern. Aggressiveness is an important endophenotype for aggression and suicidal behavior, having a heritability of around 50%. Exploration of classical candidate genes, involved in serotoninergic and dopaminergic neurotransmission, has identified few consistent risk factors for aggressiveness. miRNAs are a novel class of molecules with a growing role in normal neural function and neuropsychiatric disorders; of special interest, miR-124 is a brain-specific miRNA that is key for neuronal plasticity. We evaluated the hypothesis that a functional polymorphism in MIR124-1 gene might be associated with aggressiveness in a Colombian sample.
The Spanish adaptation of the refined version of the Aggression Questionnaire and the abbreviated Barratt Impulsiveness Scale were applied to 170 young subjects. The functional SNP in MIR124-1 (rs531564) was genotyped by a TaqMan assay.
We found a significant association between the MIR124-1 and aggressiveness in our sample, with G/G carriers having lower scores (P=0.01). This association seemed to be specific for aggressiveness, as it was not significant for impulsiveness.
We showed for the first time the association of a functional polymorphism in MIR124-1 and aggressiveness. Known targets of miR-124 (such as BDNF and DRD4 genes) could explain the effect of this miRNA on behavior. A future analysis of additional novel functional polymorphisms in other brain expressed miRNAs could be useful for a deeper understanding of aggression in humans.
人际暴力和自杀是全世界导致发病率和死亡率的主要原因之一。在一些发展中国家，如哥伦比亚，它们是公众健康关注的前五个实体之一。攻击性是攻击和自杀行为的一个重要的表型，其遗传性约为 50%。对涉及 5-羟色胺能和多巴胺能神经递质的经典候选基因的探索，仅确定了少数攻击性的一致风险因素。miRNA 是一类新的分子，在正常神经功能和神经精神疾病中具有越来越重要的作用；特别是，miR-124 是一种大脑特异性 miRNA，是神经元可塑性的关键。我们评估了这样一个假设，即 MIR124-1 基因的一个功能性多态性可能与哥伦比亚样本中的攻击性有关。
对 170 名年轻受试者应用了经过改良的攻击性问卷的西班牙语版本和简化版的巴瑞特冲动量表。通过 TaqMan 分析对 MIR124-1 中的功能性 SNP(rs531564)进行了基因分型。
我们发现 MIR124-1 与我们样本中的攻击性之间存在显著关联，G/G 携带者的评分较低（P=0.01）。这种关联似乎是针对攻击性的，因为它在冲动性方面没有统计学意义。
我们首次显示了 MIR124-1 中的功能性多态性与攻击性之间的关联。miR-124 的已知靶标（如 BDNF 和 DRD4 基因）可以解释这种 miRNA 对行为的影响。对其他大脑表达 miRNA 中额外新的功能性多态性的进一步分析可能有助于更深入地了解人类的攻击性。
