Analysis of the blood plasma ACE level of other populations and in individuals with different genotypes demonstrated that the homozygotes for the D allele had the highest levels and also an increased risk of developing CAD and MI [14,16,17]. However, the results are controversial and do not provide a clear understanding of the role of this polymorphism in the genesis of these diseases [41,42].

We found that the R219K polymorphism of the ABCA1 gene correlated with the incidence of angina, with LDL-C levels and especially with parameters affecting sclerosis of the coronary arteries in the patient group. The K219K and R219K genotypes were associated with more severe atherosclerotic lesions of the coronary arteries than the R219R genotype. In addition, allele 219K and its related genotypes were associated with higher risks for CAD by itself, and for angina and arterial hypertension in the sibling group.

 Many studies are available with analyses of different polymorphism of ABCA1 gene. Clee et al. [25] investigated phenotypic effects of the R219K polymorphism in Dutch subjects with confirmed CAD. Carriers of the 219K allele had reduced severity of atherosclerosis and fewer coronary events. The 219K allele was associated with decreased TGs and a trend to increased HDL level. Sun et al. [43] investigated the association of the R219K polymorphism and the susceptibility to CAD in Chinese population. Genotypes were determined in 248 CAD-free controls and 224 CAD cases. Carriers of the 219K allele (R219K and K219K genotypes) had a significantly decreased risk for CAD compared with wild-type genotype R219R. Plasma HDL-C in 219K allele carriers was higher than those in 219K non carriers. Similar results have been reported from Germany [44]. Balcerzyk et al. [45] did not show any association between the R219K polymorphism of the ABCA1 gene and CAD, but revealed that it acts cumulatively and synergistically with the G.C polymorphism in intron 7 of the PPARA gene in determining the risk of CAD. Here, in our Russian population, carriers of allele 219K and its related genotypes, were associated with higher risks for CAD by itself and also for angina and arterial hypertension. These contrary data suggest that the R219K polymorphism is probably a marker which is associated with other functionally significant polymorphisms that influence CAD.

There were very significant associations between the R1587K genotype and the risk of developing CAD, MI and angina among the siblings of patients with CAD. Thus, the increased risk of CAD and its main manifestations is associated with the R1587 allele. The RR for developing CAD in the carriers of genotypes R1587R and R1587K was 4.88 (95% CI 4.14-7.62). Evidently, the rare allele 1587K is protective and reduces the risk of CAD. Such a correlation has not been described previously. Clee et al. [25] did not find any correlation of this polymorphism with CAD or with the characteristics of athero sclerotic vessel lesions (such as effective arterial diameter or minimum arterial diameter) for a Dutch population. In addition, there was no association of the R1587K polymorphism with MI among populations in Northern Ireland or Scotland [4]. Clearly, there are ethnic differences in the influence of the R1587K polymorphism on the risk of developing CAD.

The association of the R1587K polymorphism with CAD in our sample was not connected to its effect on plasma lipid levels. An association between plasma lipid level and the R1587K ABCA1 gene variants was described by Clee et al. [25]. In a Danish population, low HDL-C levels were found in patients with K1587K and R1587K genotypes (which lowers the risk of developing CAD in our Russian population). Only an association of the R1587K polymorphism with apoA1 level was found in samples from Glasgow and Belfast [4]. Therefore, the association between the R1587K polymorphism and plas ma lipid spectrum may be population-specific. This suggests that the R1587K polymorphism may be an independent genetic marker of CAD risk and MI for Russians with a family history of cardiovascular diseases.

It is especially interesting that this R1587K polymorphism was not in significant linkage disequilibrium with other ABCA1 gene polymorphic sites, in particular with the R219K polymorphic site [25]. These two polymor phisms are localized in different regions of the ABCA1 gene and possibly determine different functions of ABCA1 protein. Further research conducted in a large group of patients should help clarify the importance of this association in different populations.

Our analyses did not reveal any significant correlations between the M235T polymorphism of the AGT gene and higher risk of CAD development. Moreover, Rodrigues-Perez et al. [46] detected that the 235T allele was significantly more frequent in patients with CAD than in controls. Buraczynska et al. [47] revealed that the T235T genotype of the AGT gene M235T polymorphism was associated with an increased risk of CAD and MI. At the same time, Sekuri et al. [48] demonstrated that increased premature CAD risk is associated with higher frequencies of the AGT M235M genotype. No evidence was found for an association of the eNOS minisatellite 4a/4b polymorphism with CAD in our research and in investigations by Gardemann et al. [49]. However, another polymorphism of this gene was found to be associated with CAD and MI [49,50]. Schneider et al. [51] supposed that the observed association between the Glu258Asp polymorphism of the eNOS gene and various cardiovascular disorders could be explained on the basis of altered endothelium-dependent vasodilatation. However, they did not reveal a major effect of the Glu258Asp polymorphism of the eNOS gene on endothelium-dependent vasodila tation.

These contrary data suggest that the mechanism of CAD development still remains completely unknown. Future analyses will promote our deeper understanding of the contribution of genetic factors to the pathogenesis of the disease.