title: Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.
abstract: BACKGROUND
  Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs.
  
  
  METHODS
  An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework.
  
  
  RESULTS
  IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39).
  
  
  CONCLUSIONS
  The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.
authors.affiliation: School of Surgery and Pathology, University of Western Australia.
authors.forename: L
authors.initials: L
authors.lastname: Smallwood
authors.forename: R
authors.initials: R
authors.lastname: Allcock
authors.forename: F
authors.initials: F
authors.lastname: van Bockxmeer
authors.forename: N
authors.initials: N
authors.lastname: Warrington
authors.forename: L J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: B
authors.initials: B
authors.lastname: Iacopetta
authors.forename: P E
authors.initials: PE
authors.lastname: Norman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6