Landolt Hans Peter
1 Institut für Pharmakologie und Toxikologie, Universität Zürich.
2 Klinischer Forschungsschwerpunkt Sleep & Health, Universität Zürich.
Praxis (Bern 1994). 2016 May 11;105(10):563-8. doi: 10.1024/1661-8157/a002352.
The prevalence of the insomnia syndrome and the effects of caffeine on sleep are in part genetically determined. Pharmacogenetic studies in humans demonstrate that functional polymorphisms of the genes encoding adenosine A2A receptors and dopamine transporters contribute to individual differences in impaired sleep quality by caffeine. The A2A receptor and dopamine transporter are preferentially expressed in the striatum. Together, these observations suggest that the striatum plays an important role in sleep-wake regulation. Individual caffeine sensitivity and A2A receptor genotype should be taken into account in the development of possible novel adenosine-based pharmacotherapies of sleep-wake disorders and neurodegenerative disorders such as Parkinson's disease. This may permit the prediction of individual drug effects and improve the reliability of clinical trials.
失眠综合征的患病率以及咖啡因对睡眠的影响部分由基因决定。对人类的药物遗传学研究表明，编码腺苷A2A受体和多巴胺转运体的基因的功能性多态性导致了咖啡因对睡眠质量损害的个体差异。A2A受体和多巴胺转运体在纹状体中优先表达。这些观察结果共同表明，纹状体在睡眠-觉醒调节中起重要作用。在开发可能的基于腺苷的治疗睡眠-觉醒障碍和神经退行性疾病（如帕金森病）的新型药物疗法时，应考虑个体对咖啡因的敏感性和A2A受体基因型。这可能有助于预测个体药物疗效并提高临床试验的可靠性。
