title: Combined "pro-atherosclerotic" variants of the ACE and APOE genes increase the risk of the coronary artery disease associated with the presence of cigarette smoking.
abstract: OBJECTIVE
  Cigarette smoking increases the synthesis of angiotensin-1 converting enzyme (ACE) and induces oxidative modifications of the apolipoprotein E (apo E).Thus we explored the gene-environment interactions between APOE gene epsilon and ACE gene insertion/deletion polymorphisms and cigarette smoking in coronary artery disease (CAD) patients.
  
  
  METHODS
  We analysed 360 subjects: 171 CAD patients and 189 blood donors without a history of cardiovascular diseases. ACE and APOE polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, respectively. To determine gene-environment interactions, epidemiological methodology was used.
  
  
  RESULTS
  The ACE DD genotype was a rather weak risk factor of CAD in the analysed population (OR = 1.87, P = 0.01).The differences in allele and genotype distribution of the APOE polymorphism were not statistically significant.The carriers of the combined genotype ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) were more frequent in patients, however, the differences were on the bound of statistical significance (P = 0.08). Logistic regression analysis showed that the ACE(DD) + apo E(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) cigarette smokers were much more frequent in the CAD group (OR = 11.68, 95%CI; 1.52-246.43, P = 0.009).We confirmed these results using the 4 x 2 table approach and we found a synergistic effect of the ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) combined genotype and cigarette smoking (SI = 10.52, SIM = 6.09).
  
  
  CONCLUSIONS
  We demonstrated the existence of the synergistic effect between cigarette smoking and the contemporaneous carrier-state of APOE epsilon4 and ACE D alleles which increased the risk of CAD to a large extent.
authors.affiliation: Department of Biochemistry and Medical Genetics, Medical University of Silesia, Katowice, Poland. biogen@slam.katowice.pl
authors.forename: Iwona
authors.initials: I
authors.lastname: Zak
authors.forename: Pawel
authors.initials: P
authors.lastname: Niemiec
authors.forename: Anna
authors.initials: A
authors.lastname: Balcerzyk
authors.forename: Jolanta
authors.initials: J
authors.lastname: Krauze
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D007703:Peptidyl-Dipeptidase A