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Document Details : 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 Author(s): I. Zak , P. Niemiec , A. Balcerzyk , J. Krauze Journal: Acta Cardiologica Volume: 63    Issue: 6   Date: 2008    Pages: 741-747 DOI: 10.2143/AC.63.6.2033392 Abstract : Objective — Cigarette smoking increases the synthesis of angiotensin-I 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 ACEDD + APOEε4ε4,ε3ε4,ε2ε4 were more frequent in patients, however, the differences were on the bound of statistical significance (P = 0.08). Logistic regression analysis showed that the ACEDD + apo Eε4ε4,ε3ε4,ε2ε4 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 ACEDD + APOEε4ε4,ε3ε4,ε2ε4 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 ε4 and ACE D alleles which increased the risk of CAD to a large extent.