title: Genetic polymorphisms in the aryl hydrocarbon receptor-signaling pathway and sleep disturbances in middle-aged women.
abstract: OBJECTIVE
  We aimed to determine if selected genetic polymorphisms in the aryl hydrocarbon receptor (AHR)-signaling pathway and circadian locomotor output cycles kaput (CLOCK) are associated with insomnia and early awakening in middle-aged women.
  
  
  METHODS
  Women aged 45 to 54years (n=639) were recruited into a middle-aged health study and agreed to complete questionnaires and donate blood samples. Questionnaires were used to assess sleep outcomes. Blood samples were processed for genotyping for the selected polymorphisms: AHR (rs2066853), AHR repressor (AHRR) (rs2292596), aryl hydrocarbon nuclear translocator (ARNT) (rs2228099), and CLOCK (rs1801260). Data were analyzed using multivariable logistic regression.
  
  
  RESULTS
  Women heterozygous for the AHRR alleles (GC) had decreased odds of insomnia compared to women homozygous for the AHRR_C allele (adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.49-0.96). Women with at least one of the AHRR_G or CLOCK_C alleles had significantly decreased odds of insomnia compared to women homozygous for the AHRR_C and CLOCK_T alleles (aOR, 0.64; 95% CI, 0.43-0.96). Additionally, women homozygous for the AHRR_G and CLOCK_C alleles had significantly decreased odds of insomnia compared to women homozygous for the AHRR_C and CLOCK_T alleles (aOR, 0.56; 95% CI, 0.35-0.89). None of the selected single nucleotide polymorphisms (SNPs) or combinations of SNPs were significantly associated with early awakening.
  
  
  CONCLUSIONS
  Selected genetic polymorphisms in the AHR-signaling pathway (i.e., AHRR) and CLOCK may play a role in decreasing the risk for experiencing insomnia during the menopausal transition.
authors.affiliation: Comparative Biosciences, University of Illinois, Urbana, IL, USA.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Ziv-Gal
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
authors.forename: Megan M
authors.initials: MM
authors.lastname: Mahoney
authors.forename: Susan R
authors.initials: SR
authors.lastname: Miller
authors.forename: Howard A
authors.initials: HA
authors.lastname: Zacur
authors.forename: Lisa
authors.initials: L
authors.lastname: Gallicchio
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008593:Menopause / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C111235:AHR protein, human; C492162:AHRR protein, human; C538943:CLOCK protein, human
keywords: AHR; CLOCK; Early awakening; Insomnia; Middle-aged women; Polymorphism