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Polymоrphic lоcus RS17577 оf MMP9 gеne is assоciated with еssential hypеrtension in mеn

[Original research]
Maria Ivanovna Moskalenko; Irina Vasilievna Ponomarenko; Alexey Polonikov; Mikhail Ivanovich Churnosov;

In 564 men with EH and 257 controls analysis of the polymorphic loci of metalloproteinases rs243865 MMP2, rs17577 MMP9, rs652438 MMP12 was performed using real-time PCR. It was found that the allele G (OR=1.32, p=0.04) and the genotype GG (OR=1.42, p=0.03) rs17577 of the MMP9 gene are risk factors for the development of EH. The locus rs17577 MMP9 is nsSNP (SIFT Score=0.02). This polymorphism is located in histones region marking promoters and enhancers, in the region of hypersensitivity to DNAse-1 and in the binding sites of regulatory proteins GABP, CTCF, HAE2F1 and ZNF263. Polymorphic locus rs17577 MMP9 influences the expression level of the SLC12A5 and SNX21 genes. The data obtained open up prospects for the development of new technologies for the early diagnosis and prevention of essential hypertension in men.


1. Britov A. N., Pozdnyakov Y. M. Cardiovascular prevention. National recommendations. VNOK. Kardiovaskulyarnaya terapiya i profilaktika. – Cardiovascular Therapy Prevention. 2011;10(6):57. (In Russ.).
2. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet. 2017;389(10064):37-55. https://doi.org/10.1016/S0140-6736(16)31919-5
3. Quan H., Chen G., Walker R. L., Wielgosz A., Dai S. [et al.]. Incidence, cаrdiоvаsculаr cоmрlicаtiоns аnd mоrtаlitу оf hурertensiоn bу sex аnd ethnicitу. Heаrt. Hурertensiоn Оutcоme аnd Surveillаnce Teаm. 2013;99(10):715-721. https://doi.org/10.1136/heartjnl-2012-303152
4. Okayama M., Takeshima T., Harada M., Ae R., Kajii E. Dоes а medicаl histоrу оf hурertensiоn influence disclоsing genetic testing results оf the risk fоr sаltsensitive hурertensiоn, in рrimаrу cаre? Int. J. Gen. Med. 2016;9:257-266. https://doi.org/10.2147/IJGM.S111337
5. Moskalenko M. I. The involvement of genes of matrix metalloproteinases in the development of arterial hypertension and its complication (review). Nauchny rezultat. Meditsina i farmatsiya. – Research Result. Medicine and Pharmacy. 2018;4(1):53-69. (In Russ.). https://doi.org/10.18413/2313-8955-2018-4-1-53-69
6. Olsen V., Rohde L. E., Beck-da-Silva L., Santos K. G., Biolo A. [et al.]. QRS widening rаtes аnd genetic роlуmоrрhisms оf mаtrix metаllорrоteinаses in а cоhоrt оf раtients with chrоnic heаrt fаilure. Cаn. J. Cаrdiоl. 2014;30(3):345-351. https://doi.org/10.1016/j.cjca.2013.11.014
7. Duellman T., Warren C. L., Peissig P., Wynn M., Yang J. Matrix metalloproteinase-9 genotype as a potential genetic marker for abdominal aortic aneurysm. Circulation Cardiovascular genetics. 2012;5(5):529-537. https://doi.org/10.1161/CIRCGENETICS.112.963082
8. Sun H. W., Li C. J., Chen H. Q., Lin H. L., Lu H. X. [et al.]. Involvement of integrins, MAPK, and NF-kappaB in regulation of the shear stress-induced MMP-9 expression in endothelial cells. Biochem. Biophys. Res. Commun. 2007;353(1):152-158. https://doi.org/10.1016/j.bbrc.2006.12.002
9. Mishra A., Srivastava A., Mittal T., Garg N., Mittal B. Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients. Clin. Chim. Acta. 2012;413(19-20):1668-1674. https://doi.org/10.1016/j.cca.2012.05.012
10. Sakowicz A., Fendler W., Lelonek M., Sakowicz B., Pietrucha T. Genetic polymorphisms and the risk of myocardial infarction in patients under 45 years of age. Biochemical Genetics. 2013;51(3-4):230-242. https://doi.org/10.1007/s10528-012-9558-5
11. Sorokina I. N., Rudykh N. A., Bezmenova I. N., Polyakova I. S. Population genetic characteristics and genetic epidemiological research of candidate genes associations with multifactorial diseases. Nauchnye rezultaty biomeditsinskikh issledovany. – Research Results in Biomedicine. 2018;4(4):20-30 (In Russ.). https://doi.org/10.18413/2313-8955-2018-4-4-0-3
12. Moskalenko M. I., Milanova S. N., Ponomarenko I. V. [et al.]. Study of associations of polymorphism of matrix metalloproteinases genes with the development of arterial hypertension in men. Kardiologiia. – Cardiology. 2019;59(7S):28-35. (In Russ.). https://doi.org/10.18087/cardio.2598
13. Ward L. D., Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 2016;44:877-881. https://doi.org/10.1093/nar/gkv1340
14. The GTEx Consortium. Genetic effects on gene expression across human tissues. Nature. 2017;550:204-213. https://doi.org/10.1038/nature24277
15. Djuric T., Zivkovic M., Stankovic A., Mecanin S., Alavantic D. Endothelial NOS G894 T and MMP-3 5A/6A gene polymorphisms and hypertension in Serbian population. J. Clin. Lab. Anal. 2005;19:241-246. https://doi.org/10.1002/jcla.20085
16. Giannakos E., Vardali E., Bartekova M., Fogarassyova M., Barancik M., Radosinska J. Changes in activities of circulating MMP-2 and MMP-9 in patients suffering from heart failure in relation to gender, hypertension and treatment: a cross-sectional study. Physiol. Res. 2016;19(65):149-152.
17. Alehagen U., Olsen R. S., Lаnne T., Matussek A., Wаgsаter D. PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men. BMC Medical Genetics. 2016;17(1):62. https://doi.org/10.1186/s12881-016-0325-z
18. Moskalenko M. I., Ponomarenko I. V., Polonikov A. V., Zhernakova N. I., Efremova O. A., Churnosov M. I. The role of the stress factor in the realization of the genetic predisposition to the development of stroke in patients with essential hypertension. Zhurnal Nevrologii i Psikhiatrii im. S. S. Korsakova. – S. S. Korsakov Journal of Neurology and Psychiatry. 2019;119(3/2):11-17. (In Russ.). https://doi.org/10.17116/jnevro201911903211
19. Azarova Y. E., Klyosova E. Y., Konoplya A. I. The role of polymorphisms of glutamatecysteine ligase in type 2 diabetes mellitus susceptibility in Kursk population. Nauchny rezultat. Meditsina i farmatsiya. – Research Result. Medicine and Pharmacy. 2018;4(1):39-52 (In Russ.). https://doi.org/10.18413/2313-8955-2018-4-1-39-52
20. Metzger I. F., Luizon M. R., Lacchini R., Tanus-Santos J. E. Genetic variants in matrix metalloproteinase-9 gene modify metalloproteinase-9 levels in black subjects. DNA Cell Biol. 2012;31(4):504-510. https://doi.org/10.1089/dna.2011.1388
21. Simino J., Shi G., Arnett D., Broeckel U., Hunt S. C., Rao D. Variants on Chromosome 6p22.3 Associated with Blood Pressure in the HyperGEN Study: Followup of FBPP Quantitative Trait Loci. Am. J. Hypertens. 2011;24(11):1227-1233. https://doi.org/10.1038/ajh.2011.140
22. Polonikov A., Rymarova L., Klyosova E. Volkova A., Azarova I., Bushueva O. Matrix metalloproteinases as target genes for gene regulatory networks driving molecular and cellular pathways related to a multistep pathogenesis of cerebrovascular disease. J. Cell Biochem. 2019;1:1-16. https://doi.org/10.1002/jcb.28815

Keywords: essential hypertension, matrix metalloproteinases, single nucleotide polymorphism

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy