The role of genetic factors in the pathogenesis of multifocal atherosclerosis, influence on prognosis and treatment results
Abstract
The aim of the study is to study the role of genetic markers involved in the regulation of pathways associated with inflammation, endothelial function, lipid metabolism, hemostasis in the pathogenesis of multifocal atherosclerosis, their impact on the prognosis and treatment outcomes.
Material and methods. The study is a retrospective analysis of data (genetic, clinical, instrumental and laboratory parameters) of 96 patients with stable coronary artery disease, including 10 patients with multifocal atherosclerosis, who underwent myocardial revascularization procedures, as well as interventions on other vascular regions, who were monitored for 6.4±0.54 years. Genetic testing for carriage of 68 SNPs of 37 candidate genes involved in the regulation of various pathophysiological pathways was performed: CRP (rs3093059, rs3093062, rs1417938, rs1800947, rs1130864), TNF-SF (rs385064), LTα (rs1800797), Kalirin (rs7620580), p22 (phox) (rs4673), Stromelysin-1 (rs3025058), P-selectin (rs6136, rs3093030), LTA4H (rs2660899), TLR4 (rs1554973), CCRL2 (rs6808835, rs6971599), CCR2 (rs2227010), CCR5 (rs746492, rs1799988, rs2097285); LPA (rs1853021), APOC3 (rs2854116; rs4520; rs5128), LPL (rs268; rs285; rs328; rs1801177; rs2083637; rs10096633, rs1800590), PON1 (rs854560; rs662), ABCA1 (rs 2740483; rs1800977, rs2230806), PCSK9 (rs505151), APOA5 (rs964184), LRP1 (rs5174), ANGPTL3 (rs10889353), TRIB1 (rs29540029), XKR6-AMAC1L2 (rs78194412), APOE (rs405509; rs429358+rs7412), OLR1 (rs1050283); ACE (rs4341), AGT (rs5050, rs699, rs4762), ADRB1 (rs1801253, rs1801252), EDN1 (rs10478694, rs5370), ENDRA (rs1801708), p22 (phox) (rs4673); MTHFR (rs1801133), SERPINE-1 (rs2227631), F2 (rs1799663), F5 (rs6025), F2R (rs6313), FGB (rs1800787, rs2227401, rs2042642, rs5918), vWF (rs2239159, rs2239162, rs 7969672, rs2270152).
Results. The relationship with the risk of multifocal atherosclerosis was shown by the carriage of the AG genotype of SNP LRP1 rs5174 (the gene of protein-1, similar to the low-density lipoprotein receptor). The carriage of this genotype increases the risk of developing multifocal atherosclerosis by 5.3 times (OR=5.3; 95%CI: 1,06- 26,4; χ2=5,25 p=0,05). Univariate analysis revealed associations with the risk of developing MACE with carriage of the following genetic markers: carriage of the CT genotype LPL rs10096633 (OR=5.7; 95% CI: 1.7-18.8; 2χ =15.7; p=0.0001); the AA genotype ENDRA rs1801708 (OR=5.9; 95%CI: 1.7-131.9; χ2=9.66; p=0.008); the GG genotype MTHFR rs1801133 (OR=2.65; 95%CI: 1.1-7.6; χ2=6.34; p=0.04); genotype GG CCR5 rs1799988 (OR=2.8; 95%CI:1.1-7.55; χ2=5.12; p=0.07); CC genotype CCR5 rs746492 (OR=3.3; 95%CI:1.28-9.39; χ2=6.0; p=0.03).
Conclusion. The results of the study may potentially serve as a basis for developing new therapeutic approaches to the prevention and treatment of atherosclerosis, and the established genetic risk associations may be used to assess the prognosis in patients with atherosclerotic cardiovascular diseases.
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