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.

journal_name

Acta Cardiol

journal_title

Acta cardiologica

authors

Zak I,Niemiec P,Balcerzyk A,Krauze J

doi

10.2143/AC.63.6.2033392

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

741-7

issue

6

eissn

0001-5385

issn

1784-973X

journal_volume

63

pub_type

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