title: Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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
  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.
  
  
  RESULTS
  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).
  
  
  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.
authors.affiliation: 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.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Schröder
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Primeau
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Hallmayer
authors.forename: Laura C
authors.initials: LC
authors.lastname: Lazzeroni
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Hubbard
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Hara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D017286:Polysomnography; D012044:Regression Analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012891:Sleep Apnea Syndromes / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR; OSA; aging; sleep; sleep apnea