Serotonin transporter polymorphism is associated with increased apnea–hypopnea index in older adults

Abstract

Rationale 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. Objectives 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. Methods and Measurements 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. Main Results The 5-HTT l allele was significantly associated with AHI (p=0.019), with l allele carriers displaying a higher Apnea-Hypopnea Index 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). Conclusions 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.

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature

“…Also, in older Caucasian, the L allele was associated with a higher AHI and a longer time spent during sleep at oxygen desaturation levels below 90%, as Schroder et al have demonstrated. 78 The L/S genotype is associated with moderate serotonin reuptake activity and is also more frequent in male patients, which can also explain the high prevalence of OSA in male patients, especially in those with an absent L/L genotype. There is an indirect proof that the presence of S allele is a protective factor against OSA.…”

“…Meanwhile, the 12/12 genotype was more frequent in male controls and the 12/10 genotype was overrepresented in male patients. 78 Contrarily, the study of Yue et al suggested that allele L of 5-HTTLPR and allele 10 of 5-HTTVNTR are susceptible factors for OSA in male patients. 15…”

Effects of body mass index-related disorders on cognition: preliminary results

“…Participants were 67 community-dwelling older adults recruited through advertisements and local senior centers for the investigation of sleep and behavioral outcomes. 20 These participants had also previously been genotyped and also had completed the RAVLT.…”

Common Genetic Variants Associated with Resting Oxygenation in Chronic Obstructive Pulmonary Disease

“…On the other hand, there have been few investigations into the genetics of oxygen saturation in other respiratory diseases, and these have mainly been restricted to candidate gene studies. Schroder and colleagues (25) found evidence for association of serotonin transporter polymorphism with decreased arterial oxygen saturation, and also with increasing apnea-hypopnea index in older adults. de Lima Marson and colleagues (26) searched for cystic fibrosis modifier genes by assessing genetic interactions with cystic fibrosis transmembrane conductance regulator gene mutations, but did not find a significant association with oxygen saturation itself.…”