Aging Research Center (ARC), Karolinska Institute and Stockholm University, Gävlegatan 16, 113 30, Stockholm, Sweden.
Brain Struct Funct. 2018 Jul;223(6):2653-2662. doi: 10.1007/s00429-018-1650-0. Epub 2018 Mar 21.
Dopaminergic neuromodulation is critically important for brain and cognitive integrity. The DRD2/ANKK1 Taq1A polymorphism is associated with striatal dopamine (DA) D2 receptor availability. Some previous studies have found that the A allele of the Taq1A polymorphism influences brain structure, but the results are inconsistent, likely due to population heterogeneity and small sample sizes. We investigated the genetic effect on caudate volume in a large sample of older adults without dementia. Results show that A-allele carriers have smaller caudate volume compared to non-carriers in relatively older adults (n = 167; Mage = 77.8 years), whereas the genotype did not influence caudate volume in a younger age group (n = 220; Mage = 62.8 years). Cognitive performance was not significantly affected by the DRD2 gene. Our findings extend previous observations by showing magnified genetic effects on brain volume in old age, and provide evidence for a link between a DA-related genetic polymorphism and grey matter volume in a brain region within the nigrostriatal dopaminergic pathway.
多巴胺能神经调节对大脑和认知完整性至关重要。DRD2/ANKK1 Taq1A 多态性与纹状体多巴胺（DA）D2 受体的可用性有关。一些先前的研究发现，Taq1A 多态性的 A 等位基因影响大脑结构，但结果不一致，可能是由于人群异质性和样本量小。我们在没有痴呆的老年人大样本中研究了遗传对尾状核体积的影响。结果表明，与非携带者相比，A 等位基因携带者在年龄较大的人群中（n=167；Mage=77.8 岁）尾状核体积较小，而在年龄较小的人群中（n=220；Mage=62.8 岁），基因型并不影响尾状核体积。认知表现不受 DRD2 基因的显著影响。我们的发现通过显示老年人大脑体积的遗传效应放大，扩展了先前的观察结果，并为与黑质纹状体多巴胺能通路内脑区的灰质体积相关的多巴胺相关遗传多态性之间的联系提供了证据。
