title: Genetic polymorphisms of TP53 and FAS promoter modulate the progression of coronary artery disease after coronary artery bypass grafting: a gender-specific view.
abstract: BACKGROUND
  Progression of coronary artery disease (CAD) after primary coronary artery bypass grafting (CABG) is frequent and may lead to recurrent symptoms. Various data indicate that apoptosis is the main event occurring during development and progression of atherosclerotic plaque. Plaque vascular smooth muscle cells (VSMCs) are more sensitive than regular VSMCs to TP53-mediated apoptosis.
  
  
  METHODS
  We investigated EDTA blood of 192 patients (18% female, age 60.9 ± 7.4 years) who had primary CABG more than 5 years ago. CAD progression was defined as clinical endpoints: re-operation (n = 88; 46%), catheter re-intervention (n = 58; 30%), or angina at follow-up (n = 89; 46%). Apoptotic gene polymorphisms (Toll-like receptor 2 A753G, FAS ligand C-844T, FAS promoter G-670A, TP53 Arg72Pro, and CD14 C-260T) were investigated by PCR-RFLP and compared to healthy controls (n = 200, 24% female, age 63.4 ± 5.4). Gender-specific analysis was carried out.
  
  
  RESULTS
  Heterozygous, homozygous and wild-type expression of all five genetic polymorphisms showed almost identical distribution between patients with CAD and healthy controls. Looking at clinical endpoints, with GG expression of Toll-like receptor 2 polymorphism and GG expression of FAS promoter polymorphism, results showed a relative increased risk (p = 0.09) for recurrent symptoms and re-intervention. Patients with FAS promoter polymorphism with AA expression had an increased risk of suffering from recurrent symptoms (n = 28, p = 0.04). We found that patients with homozygous expression of TP53 polymorphisms (n = 3, all male) were prone to needing re-intervention after prior CABG (p = 0.03), but not re-operation. Over a period up to 15 years, the re-intervention rate was significantly different in homozygous genotypes of FAS LG, FAS promoter and TP53.
  
  
  CONCLUSIONS
  Patients presenting with polymorphisms of FAS LG, FAS promoter and TP53 have an increased risk of CAD progression, as they have a higher rate of re-interventions.
authors.affiliation: Department of Cardiac Surgery, Ludwig Maximilians University Munich, Marchioninistr. 15, 81366, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Beiras-Fernandez
authors.forename: M K
authors.initials: MK
authors.lastname: Angele
authors.forename: C
authors.initials: C
authors.lastname: Koutang
authors.forename: P
authors.initials: P
authors.lastname: Lohse
authors.forename: B
authors.initials: B
authors.lastname: Reichart
authors.forename: P
authors.initials: P
authors.lastname: Lohse
authors.forename: S
authors.initials: S
authors.lastname: Eifert
mesh_terms: D000368:Aged; D017209:Apoptosis; D001026:Coronary Artery Bypass / Q000379:methods*; D003324:Coronary Artery Disease / Q000235:genetics*; D018450:Disease Progression; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
chemical_list: D053222:Fas Ligand Protein; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor