title: Association of GABA(B)R1 receptor gene polymorphism with obstructive sleep apnea syndrome.
abstract: OBJECTIVE
  GABA(B)R (gamma-amino butyric acid B receptor)-mediated neurotransmission has been implicated in the pathophysiology of a variety of neuropsychiatric disorders. GABA(B)R1 gene variants were identified by single-strand conformation analysis. The nucleotide exchanges cause a substitution of alanine to valine in exon 1a1 (Ala20Val), a substitution of glycine to serine in exon 7 (Gly489Ser) and a silent C to G nucleotide exchange encoding the amino acid phenylalanine in exon 11 (Phe658Phe). The significance of GABA(B)R1a gene polymorphism in obstructive sleep apnea syndrome (OSAS) as well as the association of these polymorphisms with the polysomnography findings in OSAS patients are not known. In this study, we aimed to assess the significance of 3 different GABA(B)R1 gene polymorphisms (Ala20Val, Gly489Ser and Phe658Phe) in OSAS.
  
  
  METHODS
  Seventy-five patients (23 female and 52 male) with OSAS and 99 healthy volunteers (51 female, 48 male) were included in the study to assess Ala20Val, Gly489Ser and Phe658Phe polymorphisms of the GABA(B)R1 gene.
  
  
  RESULTS
  For the Ala20Val variants, there was no significant difference between the genotypes and allele frequencies of the patients and controls, nor between both genders (p > 0.05). For Phe658Phe polymorphism, there was no significant difference between genotypes and allele frequencies of the patients and controls (p > 0.05). However, the C/C genotype was overrepresented and the T/C genotype was less frequent in male than female patients (p = 0.03). The C/C genotype was overrepresented and the T/C genotype was less frequent in male patients than male controls (p = 0.01). For GABA(B)R1-Gly489Ser polymorphism, all of the patients and controls had G/G genotype. The apnea arousal index scores of the male patients with C/C genotype were significantly higher than in the patients with C/T genotype (p = 0.01). The percent total sleep time in non-REM 1 scores of the male patients with T/T genotype were significantly higher than in the patients with T/C genotype (p = 0.021). The percent total sleep time in non-REM 2 scores of the female patients with C/C genotype were significantly higher than in the patients with C/T genotype (p = 0.006).
  
  
  CONCLUSIONS
  The Ala20Val polymorphism of the GABA(B)R1 gene may be associated with OSAS, whereas Gly489Ser polymorphism does not seem to be involved in OSAS. The C/C variant of the Phe658Phe polymorphism GABA(B)R1 gene seems associated with the occurrence of OSAS and is also associated with some sleep related parameters (apnea arousal index and percent total sleep time in non-REM) recorded by polysomnography.
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, Gazi University, Ankara, Turkey. bayazity@yahoo.com
authors.forename: Yildirim A
authors.initials: YA
authors.lastname: Bayazit
authors.forename: Metin
authors.initials: M
authors.lastname: Yilmaz
authors.forename: Oguz
authors.initials: O
authors.lastname: Kokturk
authors.forename: M Emin
authors.initials: ME
authors.lastname: Erdal
authors.forename: Tansu
authors.initials: T
authors.lastname: Ciftci
authors.forename: Tuba
authors.initials: T
authors.lastname: Gokdogan
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Kemaloglu
authors.forename: Fikret
authors.initials: F
authors.lastname: Ileri
mesh_terms: D000328:Adult; D000242:Cyclic AMP / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D017286:Polysomnography; D018080:Receptors, GABA-B / Q000235:genetics*; D012720:Severity of Illness Index; D012737:Sex Factors; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012894:Sleep Stages / Q000502:physiology
chemical_list: D017931:DNA Primers; D018080:Receptors, GABA-B; D000242:Cyclic AMP