Department of Neurology, Shimane University School of Medicine, 89-1, Enya-cho, Izumo 693-8501, Japan.
Neurosci Lett. 2013 Aug 9;549:87-91. doi: 10.1016/j.neulet.2013.05.075. Epub 2013 Jun 12.
Dopaminergic neurotransmission is an important factor in the pathogenesis of apathy. In addition, the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged. Therefore, we hypothesized that genes associated with brain dopaminergic activity may have some effects on apathy. In the current study, we evaluated the association between four functional single-nucleotide polymorphisms (SNPs) in specific genes related to dopaminergic neurotransmission and apathy in a general population. Participants in the health examination at the Shimane Institute of Health Science were recruited for this study (n=963). Apathy was assessed using the Japanese version of the apathy scale. SNPs were genotyped using the TaqMan method. In our population, 22.1% had apathy. We confirmed that apathy was associated with decreased cognitive function and depressive state. A significant association was found between an SNP in the catechol-O-methyltransferase (COMT) gene (rs4680) encoding the low-activity Met allele and apathy. This relationship was still significant after adjustment for confounding factors. Our study indicates an association between rs4680, an SNP in the COMT gene, and lower risk of apathy. Considering the function of rs4680, the current study suggests the importance of dopaminergic neurotransmission in the pathogenesis of apathy in a general population.
多巴胺能神经传递是淡漠症发病机制的一个重要因素。此外，遗传因素对大脑多巴胺活性的调节作用得到了广泛认可。因此，我们假设与大脑多巴胺活性相关的基因可能对淡漠症有一定的影响。在本研究中，我们评估了与多巴胺能神经传递相关的特定基因中的四个功能性单核苷酸多态性（SNP）与一般人群中淡漠症之间的关联。在岛根健康科学研究所进行健康检查的参与者被招募参加了这项研究（n=963）。使用淡漠量表的日语版本评估淡漠症。使用 TaqMan 方法对 SNP 进行基因分型。在我们的人群中，22.1%的人患有淡漠症。我们证实淡漠症与认知功能下降和抑郁状态有关。儿茶酚-O-甲基转移酶（COMT）基因（rs4680）编码低活性 Met 等位基因的 SNP 与淡漠症之间存在显著关联。在调整混杂因素后，这种关系仍然显著。我们的研究表明，COMT 基因中的 rs4680 与淡漠症的风险降低之间存在关联。考虑到 rs4680 的功能，本研究提示多巴胺能神经传递在一般人群淡漠症发病机制中的重要性。
