Impact of ACE and ApoE polymorphisms on myocardial perfusion: correlation with myocardial single photon emission computed tomographic imaging

Abstract

Coronary artery disease is associated with multiple genetic and environmental risk factors. In this study, we evaluated the correlation of angiotensin l-converting enzyme (ACE) (I/D) and ApoE gene polymorphisms (E2, E3, E4 and g.-219G/T) with myocardial perfusion. We examined 410 patients using exercise-rest myocardial perfusion single photon emission computed tomography (SPECT), in which the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) indexes were calculated. Homozygotes for the ACE D allele had greater mean values of SSS (Po0.001) and SDS (Po0.001). In addition, E3 homozygotes, E4 heterozygotes and E4 homozygotes had significantly higher values of SSS and SDS compared with E3 heterozygotes (Po0.001); E4 homozygotes had significantly higher values of SSS and SDS compared with E3 homozygotes. Furthermore, for the g.-219G4T polymorphic site at the promoter region of ApoE gene, the mean values of SSS and SDS were significantly higher for T heterozygotes/homozygotes than for GG homozygotes. Adjusting for all demographic and clinical data using multiple linear regression analysis it was found that ACE D and both ApoE genotypes were independent predictors with a cumulative contribution for the prediction of SSS and SDS. Furthermore, logistic regression analysis revealed that all three genotypes had an independent predictive ability for abnormal SSS (SSS42). These data provide the first evidence of an association and significant cumulative contribution of the aforementioned genotypes in myocardial perfusion with E4 allele having the strongest association followed by ACE D and ApoE g.-219T alleles.

Apolipoprotein E Genotype and Cardiovascular Diseases in the Elderly

“…There are very few large studies examining the role of apoe4 in relation to coronary atherosclerosis. One study of patients aged 61 years (mean) who underwent exercise-rest myocardial perfusion single positron emission computed tomography (SPECT) reported that individuals who were homozygous for e3 and e4 and individuals who were heterozygous for e4 had significantly higher values of a summed stress score (SSS) compared with those who were heterozygous for the e3 allele ( P  < 0.001) [22]. After adjustment for demographic and clinical risk factors, both APOE genotypes were independent predictors, with a cumulative contribution for the prediction of SSS and summed difference score.…”

Novel approaches for the management of coronary artery disease

“…However, we believe that a better understanding of CAD development can be achieved through the analysis of genetic information combined with functional imaging. Although Izadpanah et al did not find any association between the rs2713604 polymorphism and premature MI, we have reported the independent correlations (after adjustment for various factors, including CAD risk factors) of several gene polymorphisms with myocardial ischemia, based on stressrest myocardial single-photon emission computed tomography (SPECT) imaging [4][5][6]. In particular, polymorphisms of the following genes were investigated: factor V Leiden, factor II prothrombin, plasminogen activator inhibitor 1, β-fibrinogen, factor XIII, apolipoprotein E, angiotensin l-converting enzyme, angiotensinogen, angiotensin II type 1 receptor, angiotensin II type 2 receptor, and renin.…”

Understanding the genetics of coronary artery disease through the lens of noninvasive imaging

“…The ApoE4 gene was found to have the strongest association followed by ACED and Apog-219 T polymorphisms. [32] The combined structural and metabolic components secure a place in future of cardiovascular imaging; [116] this wealth of information, however, comes at the cost of higher levels of radiation (> 10 mSv), and lower availability. [93] The spatial resolution of PET is inherently low (4–8 mm), so that radiotracer activity in small coronary or even carotid arteries requires an additional imaging method, usually CT, to show the location of the abnormality.…”

“…Since CAD directed GWA studies began four years ago, many polymorphisms have been associated with hard endpoints of CAD, such as MI,[26,27] premature MI,[28–32] and stroke (locus 4q25). [33] Sifting through the statistical noise, however, requires selecting effective phenotypic markers.…”