The relationship between polymorphism -1612 5A/6A of the MMP3 gene and 2003G>A of the MMP9 gene and ischemic heart disease risk in the population of Central Russia

It is known that the proteolysis disorder and changes in metabolism of extracellular matrix proteins cause the process of remodeling heart muscle, which is one of the risk factors for coronary heart disease (CHD). Matrix metalloproteinases (MMPs) are responsible for the process of proteolysis. Single nucleotide substitutions in genes encoding MMPs may influence the functional activity of enzymes. The aim of this study was to investigate the association of polymorphisms -1612 5A/6A (rs3025058) of MMP3 gene and 2003G>A (rs17577) of MMP9 gene with the risk of CHD in population of Central Russia. We studied DNA samples obtained from 946 subjects, including 256 CHD patients and 248 sex- and age-matched healthy individuals. The polymorphisms were genotyped through a real-time PCR using TaqMan allele-discrimination assays. The comparative analysis showed no difference in allele and genotype frequencies of MMP3 and MMP9 polymorphisms between the case and control groups. The study showed that polymorphism -1612 5A/6A of MMP3 gene and polymorphism 2003G>A of MMP9 gene are not associated with coronary heart disease in population of Central Russia.

ишемическая болезнь сердца, наследственная предрасположенность, матриксные металлопротеиназы, ген MMP3, ген MMP9, coronary heart disease, genetic predisposition, matrix metalloproteinases, MMP3, MMP9

1. Пальцев М.А. Молекулярная медицина: достижения и перспективы // Молекулярная медицина. - 2004. - № 4. - С. 3-8.

2. Рогова Л.Н., Шестернина Н.В., Замечник Т.В., Фастова И.А. Матриксные металлопротеиназы, их роль в физиологических и патологических процессах (обзор) // Вестник новых медицинских технологий. - 2011. - Т. 18, № 2. - С. 86-87.

3. Соловьева Н.И. Матриксные металлопротеиназы и их биологические функции // Биоорганическая химия. - 1998. - Т. 24, № 4. - С. 245-255.

4. Яровая Г.А. Биорегулирующие функции и патогенетическая роль протеолиза // Лабораторная медицина. - 2003. - № 6. - С. 48-54.

5. Bornstein P., Sage E.H. Matricellular proteins: extracellular modulators of cell function // Current opinion in cell biology. - 2002. - Vol. 14, N 5. - P. 608-616.

6. Bushueva O., Solodilova M., Ivanov V., Polonikov A. Gender-specific protective effect of the - 463G>A polymorphism of myeloperoxidase gene against the risk of essential hypertension in Russians // Journal of the American Society of Hypertension. - 2015. - Vol. 9, N 11. - P. 902-906.

7. Corcoran M.L., Hewitt R.E., Kleiner Jr D.E., Stetler-Stevenson W.G. MMP-2: expression, activation and inhibition // Enzyme & protein. - 1995. - Vol. 49, N 1-3. - P. 7-19.

8. Deschamps A.M., Spinale F.G. Disruptions and detours in the myocardial matrix highway and heart failure // Current heart failure reports. - 2005. - Vol. 2, N 1. - P. 10-17.

9. Ennis B.W., Matrisian L.M. Matrix degrading metalloproteinases // Journal of neuro-oncology. - 1993. - Vol. 18, N 2. - P. 105-109.

10. Humphries S.E., Luong L.A., Talmud P.J., Frick M.H., Kesäniemi Y.A., Pasternack A., Taskinen M.-R., Syvänne M. The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study // Atherosclerosis. - 1998. - Vol. 139, N 1. - P. 49-56.

11. Kaplan R.C., Smith N.L., Zucker S., Heckbert S.R., Rice K., Psaty B.M. Matrix metalloproteinase-3 (MMP3) and MMP9 genes and risk of myocardial infarction, ischemic stroke, and hemorrhagic stroke // Atherosclerosis. - 2008. - Vol. 201, N 1. - P. 130-137.

12. Koch W., de Waha A., Hoppmann P., Schömig A., Kastrati A. Haplotypes and 5A/6A polymorphism of the matrix metalloproteinase-3 gene in coronary disease: Case-control study and a meta-analysis // Atherosclerosis. - 2010. - Vol. 208, N 1. - P. 171-176.

13. Murphy G., Cockett M.I., Stephens P.E., Smith B.J., Docherty A.J. Stromelysin is an activator of procollagenase. A study with natural and recombinant enzymes // Biochem. J. - 1987. - Vol. 248. - P. 265-268.

14. Samnegård A., Silveira A., Lundman P., Boquist S., Odeberg J., Hulthe J., Mcpheat W., Tornvall P., Bergstrand L., Ericsson C.-G., Ericsson P., Hamsten A. Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 - 1612 5A/6A promoter genotype and associated with myocardial infarction // Journal of internal medicine. - 2005. - Vol. 258, N 5. - P. 411-419.

15. Sternlicht M.D., Werb Z. How matrix metalloproteinases regulate cell behavior // Annual review of cell and developmental biology. - 2001. - Vol. 17. - P. 463.

16. Townsend N., Wickramasinghe K., Bhatnagar P., Smolina K., Nichols M., Leal J., Rayner M. Coronary heart disease statistics. - 2012 edition. - British Heart Foundation : London, 2012. - P. 107.

17. Wilson E.M., Spinale F.G. Myocardial remodelling and matrix metallotxoteinases in heart failure: turmoil within the interstitium // Annals of medicine. - 2001. - Vol. 33, N 9. - P. 623-634.

18. Wu N., Lu X., Hua Y., Song L., Ye J., Li J., Yang Y. Haplotype Analysis of the Stromelysin-1 (MMP3) and Gelatinase B (MMP9) Genes in Relation to Coronary Heart Disease // Annals of human genetics. - 2009. - Vol. 73, N 4. - P. 404-410.

19. Ye S., Eriksson P., Hamsten A., Kurkinen M., Humphries S.E., Henney A.M. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression // Journal of Biological Chemistry. - 1996. - Vol. 271, N 22. - P. 13055-13060.

20. Ye S., Watts G.F., Mandalia S., Humphries S.E., Henney A.M. Preliminary report: genetic variation in the human stromelysin promoter is associated with progression of coronary atherosclerosis // British heart journal. - 1995. - Vol. 73, N 3. - P. 209-215.