ASSOCIATION OF MOLECULAR GENETIC FACTORS WITH THE SIGNS OF ATEROSCLEROTIC PLAQUES INSTABILITY

Aim. Analysis of possible associations of polymorphisms of the urokinase system and matrix metalloproteases genes with criteria of atherosclerotic plaques instability.

Material and methods. Totally, 50 patients were investigated, with carotid atherosclerosis (32 males and 18 females). Inclusion criteria were carotid stenosis ≥70% and carotid endarterectomy. Patients were selected to groups according to macroscopic signs of instability of the lesions and thickness of fibrous cap. The groups were compared by the rates of mononucleotide polymorphisms С(-1306)Т (rs243865) gene MMP2, С(-1562)T (rs3918242) and A855G (Gln279Arg, rs17576) gene MMP9, Pro141Leu (C7240T, rs2227564) and С/T 3′-UTR (rs4065) gene PLAU, Lys220Arg (A659G, rs2302524) and T(-516)C (rs344781) gene PLAUR, (-675)4G/5G (rs1799768)gene SERPINE1.

Results. Monofactorial analysis showed the association of the variants 279Gln/Gln of gene MMP9 and 141Leu/Leu gene PLAU with development of macroscopically stable plaques. By multifactorial analysis, only the carriage of genotype 141Leu/Leugene PLAU was associated with development of stable plaques. For the group of genotype carriers 141Pro/Leu and 141Leu/Leu odds ratio is 0,22 (95% confidence interval 0,05-0,93). With the development of plaques with capsule less than 65 mcm, by monofactorial analysis, the associated variants are 3′-UTR C/T gene PLAU and (-516)T/C gene PLAUR, and normal body mass. Presence of obesity and the carriage of allele (-516) C gene PLAUR are protective against the thin cap plaques development. In patients with absent obesity and genotype (-516)T/T gene PLAUR odds ratio for the thin cap plaque occurrence is 10,16 (95% confidence interval 2,5740,16).

Conclusion. In the work, an association is shown of the polymorphism of urokinase system gene (urokinase plasminogen activator and receptor) with criteria of atherosclerotic lesion instability. Also, an association demonstrated of obesity with more stable plaques.

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