title: Cytokine gene polymorphisms in obstructive sleep apnoea/hypopnoea syndrome.
abstract: OBJECTIVE
  The pro-inflammatory cytokines, TNF-α, IL-6, and IL-8 are elevated in obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Cytokine gene interactions are complex and haplotype analysis may be more informative. We hypothesized that the effects of TNF-α in OSAHS might be due to linkage disequilibrium of the TNF-α (-308A) single nucleotide polymorphism (SNP) with other polymorphisms within the TNF-α gene, and that predisposition to elevated IL-6 and IL-8 levels in OSAHS might be attributable to pro-inflammatory IL-6 and IL-8 gene promoter polymorphisms.
  
  
  METHODS
  173 subjects were classified as having definite OSAHS or not on the basis of apnoea-hypopnoea frequency, sex, age, and symptoms. Population controls comprised 192 random UK blood donors. Genotyping was undertaken for the TNF-α promoter polymorphisms (-1031, -863, -857, -238), two lymphotoxin-α polymorphisms (intron 1 and Thr60Asn), the pro-inflammatory IL-6 gene promoter polymorphism (-174), and IL-8 gene promoter polymorphisms (-251; -781).
  
  
  RESULTS
  There was no significant difference between groups re: genotype/allelic frequency in the genes investigated. Association between disease status and the TNF-α alleles independently (TNF-103, TNF-803, TNF-857, TNF-238) with five haplotypes of TNF-α was not significant (p > 0.05). There was no difference in allelic or genotypic frequencies between obese and non-obese subjects with OSAHS. The TNF-α (-863A) allele alone, was significantly associated with obesity (OR 2.4; CI95% 1.1-5; p = 0.025).
  
  
  CONCLUSIONS
  Only the TNF-α (308A) SNP appears to be significantly associated with OSAHS. The impact of cytokine gene polymorphisms on phenotypic expression of inflammation in OSAHS is likely to be complex.
authors.affiliation: Department of Internal Diseases, Pneumology and Allergology, Warsaw Medical University, Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Bielicki
authors.affiliation: Medical Genetics Section, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: MacLeod
authors.affiliation: Department of Sleep Medicine, Royal Infirmary Edinburgh, Edinburgh, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Douglas
authors.affiliation: Department of Sleep Medicine, Royal Infirmary Edinburgh, Edinburgh, UK. Electronic address: rlriha@hotmail.com.
authors.forename: R L
authors.initials: RL
authors.lastname: Riha
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Cytokine gene polymorphisms; Interleukin-6; Interleukin-8; Lymphotoxin; Sleep apnoea; TNF-alpha haplotypes