title: Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) formation involves an inflammatory and proteolytic process. Previous studies suggest that AAA is a multifactorial disease with a strong genetic background. This study evaluated the role of seven important functional single nucleotide polymorphisms (SNPs) in AAA.
  
  
  METHODS
  This was a case-control study of two independent populations: 397 AAA patients (mean aortic diameter, 6.2 ± 1.4 cm) and 393 controls (mean diameter, 2.4 ± .2 cm) recruited from Greece (the main cohort), and 400 patients (mean diameter: 5.4 ± 1 cm) and 400 controls (mean diameter, 2.4 ± .6 cm) recruited from the United Kingdom (replication cohort). The functional SNPs analyzed were rs3025058, rs3918242, rs2276109, rs1801133, rs1799752, rs1799983, and rs16874954. These regulate the following enzymes: matrix metalloproteinases (MMPs), angiotensin-converting enzyme, endothelial nitric oxide synthase, methylenetetrahydrofolate reductase (MTHFR), and platelet-activating factor acetylhydrolase or lipoprotein-associated phospholipase A2.
  
  
  RESULTS
  Genotype distributions (univariate analyses) did not differ significantly between cases and controls in the main or the replication cohort, with the exception of the MMP-3 rs3025058 SNP, where differences were borderline significant (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.02-1.97; P = .04) in the replication cohort. Adjusted analyses for age, sex, smoking, hypertension, and hypercholesterolemia disclosed no differences in either cohort. For SNPs that had previously been associated with AAA presence, meta-analysis of currently available data together with the two study cohorts disclosed positive associations for the MMP-3 rs3025058 (OR, 1.15; 95% CI, 1.06-1.25; P = .0009) and MTHFR rs1801133 (OR, 1.07; 95% CI, 1.02-1.12; P = .0088).
  
  
  CONCLUSIONS
  The SNPs included in this analysis were not associated with AAA presence in either study population. However, meta-analysis of the currently available data disclosed a positive association for MMP-3 rs3025058 and MTHFR rs1801133.
authors.affiliation: Department of Vascular Surgery, Aristotle University, Thessaloniki, Greece; Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom. Electronic address: a_saratzis@yahoo.gr.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Saratzis
authors.affiliation: Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bown
authors.affiliation: Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Wild
authors.affiliation: Wolfson Computer Laboratory, University Hospitals Birmingham, Birmingham, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.affiliation: Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Smith
authors.affiliation: Wolfson Computer Laboratory, University Hospitals Birmingham, Birmingham, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Department of Vascular Surgery, Aristotle University, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Melas
authors.affiliation: Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom.
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D000368:Aged; D000483:Alleles; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006115:Greece; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D059748:Proteolysis; D006113:United Kingdom
chemical_list: D005819:Genetic Markers; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3