title: Association of OAZ1 gene polymorphisms with subclinical and clinical vascular events.
abstract: OBJECTIVE
  Proliferation and migration of vascular smooth muscle cells (VSMCs) are striking features shared by vascular ageing, atherosclerosis, and in-stent restenosis. VSMC biology depends in part on polyamines whose metabolism is closely regulated by ornithine decarboxylase antizyme 1 (OAZ1). Therefore, we sought for association between OAZ1 gene polymorphisms and various outcomes involving VSMC proliferation.
  
  
  RESULTS
  Systematic screening of the OAZ1 gene enabled to detect 21 variants. The impact of 4 selected tag polymorphisms (+849C/T, +851G/T, +1804G/A, and +2222A/G) was evaluated in 3 independent association studies. In a sample of 205 patients, the +2222G allele was associated with an increased risk of 6-month coronary in-stent restenosis (OR [95%CI]=2.1 [1.2 to 3.6]; P=0.0071). In a sample of 1001 subjects participating to the EVA study, the +2222G allele was longitudinally associated with a 4-year increase in common carotid intima-media thickness (P=0.047). In a case-control study (466 cases versus 466 controls), the risk of coronary heart disease associated with the +2222G allele was 1.3 (95%CI=[1.1 to 1.6]; P=0.026). No other significant association was consistently detected.
  
  
  CONCLUSIONS
  We identified the OAZ1+2222A/G polymorphism as a potential genetic marker of vascular events. Our findings strengthen the hypothesis that the polyamine metabolism plays a role in vascular diseases.
authors.affiliation: Inserm, U744, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, F-59019 Lille cedex, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dumont
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Zureik
authors.forename: Christophe
authors.initials: C
authors.lastname: Bauters
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Grupposo
authors.forename: Dominique
authors.initials: D
authors.lastname: Cottel
authors.forename: Michèle
authors.initials: M
authors.lastname: Montaye
authors.forename: Martial
authors.initials: M
authors.lastname: Hamon
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducimetière
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Thierry
authors.initials: T
authors.lastname: Brousseau
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D003327:Coronary Disease / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D023903:Coronary Restenosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology*; D016017:Odds Ratio; D010641:Phenotype; D011073:Polyamines / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D011073:Polyamines; D011506:Proteins; C031017:ornithine decarboxylase antizyme