Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; Department of Psychiatry and Behavioral Sciences, Strasbourg University Hospital and Strasbourg University, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neuroscience, Strasbourg, France; University Sleep Clinic, Department of Neurology, Strasbourg University Hospital, Strasbourg, France.
Int J Geriatr Psychiatry. 2014 Mar;29(3):227-35. doi: 10.1002/gps.3994. Epub 2013 Jun 11.
A functional polymorphism of the serotonin transporter gene (5-HTTLPR) has previously been related to upper airway pathology, but its contribution to obstructive sleep apnea (OSA), a highly prevalent sleep disorder in older adults, remains unclear.
We aimed to investigate the relationship between apnea-hypopnea index (AHI) and genetic variations in the promoter region of the 5-HTTLPR in older adults.
DNA samples from 94 community-dwelling older adults (57% female, mean age 72 ± 8) were genotyped for the 5-HTTLPR polymorphism. All participants were assessed in their homes with full ambulatory polysomnography in order to determine AHI and related parameters such as hypoxia, sleep fragmentation, and self-reported daytime sleepiness.
The 5-HTT l allele was significantly associated with AHI (p = 0.019), with l allele carriers displaying a higher AHI than s allele homozygotes. A single allele change in 5-HTTLPR genotype from s to l resulted in an increase of AHI by 4.46 per hour of sleep (95% CI, 0.75-8.17). The l allele was also associated with increased time during sleep spent at oxygen saturation levels below 90% (p = 0.014).
The observed significant association between the 5-HTTLPR l allele and severity of OSA in older adults suggests that the l allele may be important to consider when assessing for OSA in this age group. This association may also explain some of the observed variability among serotonergic pharmacological treatment studies for OSA, and 5-HTT genotype status may have to be taken into account in future therapeutic trials involving serotonergic agents.
5-羟色胺转运体基因（5-HTTLPR）的功能性多态性与上呼吸道病理有关，但它与阻塞性睡眠呼吸暂停（OSA）的关系尚不清楚，OSA 是老年人中一种高发的睡眠障碍。
本研究旨在探讨老年人群中 5-HTTLPR 启动子区域基因变异与呼吸暂停-低通气指数（AHI）之间的关系。
对 94 名居住在社区的老年人（57%为女性，平均年龄 72±8 岁）的 DNA 样本进行 5-HTTLPR 多态性基因分型。所有参与者均在家中接受全夜动态多导睡眠监测，以确定 AHI 及相关参数，如缺氧、睡眠片段化和白天嗜睡的自我报告。
5-HTT l 等位基因与 AHI 显著相关（p=0.019），l 等位基因携带者的 AHI 高于 s 等位基因纯合子。5-HTTLPR 基因型中 s 向 l 单一等位基因的改变导致每小时睡眠 AHI 增加 4.46（95%CI，0.75-8.17）。l 等位基因还与睡眠期间血氧饱和度低于 90%的时间增加相关（p=0.014）。
在老年人群中观察到的 5-HTTLPR l 等位基因与 OSA 严重程度之间的显著关联表明，在评估该年龄组的 OSA 时，l 等位基因可能是需要考虑的重要因素。这种关联也可能解释了一些观察到的与 OSA 的 5-羟色胺能药物治疗研究之间的可变性，并且在涉及 5-羟色胺能药物的未来治疗试验中，5-HTT 基因型状态可能需要考虑。
