Polymorphic locus RS11568818 of the MMP7 gene is associated with the development of essеntial hypertension in women
https://doi.org/10.15829/1560-4071-2018-10-14-17
Abstract
Aim. To study the involvement of polymorphic loci rs1799750 MMR1, rs3025058 MMR3, rs 11568818 MMR7, rs1320632 MMR8 and rs11225395 MMR8 in the development of arterial hypertension (AH) in women of the Central Chernozemny Region of Russia.
Material and methods. During the study 584 women were examined: 375 patients with AH and 209 control subjects. Analysis of metalloproteinases’ polymorphic loci was performed using real-time PCR (TagMan probes). Statistical processing of the results was performed using the STATISTICA for Windows 10.0. The regulatory potential of polymorphic loci was analyzed using the HaploReg software (v4.1). Assessment of the effects of single nucleotide polymorphisms on gene expression (cis-eQTL) was performed according to the Genotype-Tissue Expression (GTEx) project.
Results. We established that the polymorphic allele G (OR=1,49, 95% CI=1,16-1,92, p=0,002) and the GG genotype (OR=1,64, 95% CI=1,12-2,40, p=0,010) in the rs11568818 locus of MMP7 gene is associated with a high risk of AH in women. Polymorphic marker rs11568818 MMP7 has significant epigenetic effects: located in the region of histones, labeling promoters and enhancers, in the region of binding sites with transcription factors Foxa known1, PLZF, Pou5f1 known2 and GR known4, in binding niche of regulatory proteins TBP, c-FOS, c-Jun. It was found that the polymorphic variant G rs1 1568818 of MMP7 is associated with a reduced level of expression of the MMP7 gene.
Conclusion. The polymorphic locus rs11568818 of the MMP7 gene is involved in the development of AH in women of the Central Chernozemny Region of Russia.
About the Authors
M. I. Moskalenko
Medical Institute of Belgorod State University
Russian Federation
Competing Interests: The authors declare that they have no conflict of interest
Russian Federation
Moskalenko Maria Ivanovna.
Competing Interests: The authors declare that they have no conflict of interest
I. V. Ponomarenko
Medical Institute of Belgorod State University
Russian Federation
Competing Interests: The authors declare that they have no conflict of interest
Russian Federation
Ponomarenko Irina Vasilevna.
Competing Interests: The authors declare that they have no conflict of interest
A. V. Polonikov
Medical Genetics and Ecology of Kursk State Medical University
Russian Federation
Competing Interests: The authors declare that they have no conflict of interest
Russian Federation
Polonikov Aleksej Valerevich.
Competing Interests: The authors declare that they have no conflict of interest
M. I. Churnosov
Medical Institute of Belgorod State University
Russian Federation
Competing Interests: The authors declare that they have no conflict of interest
Russian Federation
Churnosov Miсhail Ivanovich.
Competing Interests: The authors declare that they have no conflict of interest
References
1. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). European Heart Journal. 2016;37(29):2315-81. doi:101093/eurheartj/ehw106.
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 191 million participants. Lancet (London, England). 2017;389(10064):37-55. doi:10.1016/S0140-6736(16)31919-5.
3. Britov AN, Pozdnyakov YM. Cardiovascular prevention. National recommendations. VNOK. Cardiovascular Therapy Prevention. 2011; 10(6):57. (In Russ.)
4. Intengan HD, Schiffrin EL. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension. 2001;38:581-7. doi:10.1161/hy09t1.096249.
5. Chen Q, Jin M, Yang F, et al. Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling. Mediators of Inflammation. 2013;2013:928315. doi:10.1155/2013/928315.
6. Dhingra R, Pencina MJ, Schrader P, et al. Relations of Matrix Remodeling Biomarkers to Blood Pressure Progression and Incidence of Hypertension in the Community. Circulation. 2009;119(8):1101-7 doi:10.1161/CIRCULATIONAHA.108.821769.
7. Moskalenko MI. The involvement of genes of matrix metalloproteinases in the development of arteial hypertension and its complication (review). Research Result. Medicine and Pharmacy. 2018;4( 1 ):53-69. (In Russ.) doi:10.18413/2313-8955-2018-4-1-53-69.
8. Ponomarenko IV. Selection of polymorphic locuses for analysis of associations in genetic-epidemiological researches. Research Result. Medicine and Pharmacy. 2018;4(2):40-54. (In Russ.) doi:10.18413/2313-8955-2018-4-2-0-5.
9. Liеvre A, Milet J, Carayol J. Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma. BMC Cancer. 2006;6:270. doi:10.1186/1471-2407-6-270.
10. Pradhan-Palikhe P, Pussinen PJ, Vikatmaa P, et al. Single nucleotide polymorphism-799C/T in matrix metalloproteinase-8 promoter region in arterial disease. Innate Immun. 2012;18(3):511-7 doi:10.1177/1753425911423852.
11. Giannakos E, Vardali E, Bartekova M, et al. 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):149-52. ISSN 1802-9973.
12. Gammelmark A, Nielsen MS, Lundbye-Christensen S, et al. Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident Myocardial Infarction: A Danish Case- Cohort Study. PLoS ONE. 2016;11(11):e0167217 doi:10.1371/journal.pone.0167217
13. Jormj S, Whatling C, Walter DH, et al. Allele-Specific Regulation of Matrix Metalloproteinase-7 Promoter Activity Is Associated With Coronary Artery Luminal Dimensions Among Hypercholesterolemic Patients. Arteriosclerosis, Thrombosis, and Vascular Biology 2001;21:1834-9. doi:10.1161/hq1101.098229.
14. Pеrez-Hernаndez N, Vargas-Alarcon G, Martinez-Rodriguez N, et al. The matrix metalloproteinase 2-1575 gene polymorphism is associated with the risk of developing myocardial infarction in Mexican patients. J Atheroscler Thromb. 2012;19(8):718-27. doi:10.5551/jat.11817.
15. Alp E, Yilmaz A, Tulmac M, et al. Analysis of MMP-7 and TIMP-2 gene polymorphisms in coronary artery disease and myocardial infarction: A Turkish case-control study. Kaohsiung J Med Sci. 2017;33(2):78-85. doi:10.1016/j.kjms.2016.12.002.
Review
For citations:
Moskalenko M.I., Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Polymorphic locus RS11568818 of the MMP7 gene is associated with the development of essеntial hypertension in women. Russian Journal of Cardiology. 2018;(10):14-17. (In Russ.) https://doi.org/10.15829/1560-4071-2018-10-14-17
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