Association of polymorphism -1171 5A/6A of the matrix metalloproteinase gene type 3 (rs35068180) with dilated cardiomyopathy

Cover Page

Cite item

Full Text

Abstract

The paper describes the investigation of matrix metalloproteinase type 3 (MMP-3) -1171 5A/6A gene polymorphic allele’s variants (rs35068180) in patients with dilated cardiomyopathy. A allele and 6А6А genotype of MMP-3 -1171 5A/6A gene (rs35068180) were determined as new genetic predictors of dilated cardiomyopathy development.

Aim. To study the association of polymorphism -1171 5A/ of the MMP-3 gene with dilated cardiomyopathy of various origins.

Material and methods. The main study group comprised 221 patients with dilated cardiomyopathy (DCM) of different origin. Their average age was 55.30±9.69 years. Among them there were 111 persons with DCM of ischemic origin, including 99 (89.2%) men and 12 (10.8%) women. The average age of the subjects with DCM was 51.73±9.74 years, the age of the male subgroup was 51.00±8.96 years, and the age of the female subgroup was 57.75±3.71 years. A total of 110 patients with idiopathic cardiomyopathy were included in the study. Among 221 patients, 110 persons did not demonstrated idiopathic dilated cardiomyopathy as the cause of myocardium dilation. This group comprised 100 (91.5%) male patients and 10 (8.5%) female patients. The control group of subjects (221 persons) was represented by healthy people without diseases of the cardiovascular system. The average age of control subjects was 53.6±4.8 years. We examined all patients in the main group using routine laboratory and instrumental methods, as well as coronary angiography. If myocarditis was suspected, we did an MRI of the heart. Genotyping of polymorphism -1171 5A/6A (rs35068180) of the MMP-3 gene was performed using PCR.

Results. Among patients of the main group with dilated myocardial remodeling of various Genesis, the allele was documented in 65.8% of cases against 59.3% among the control group, p=0.044. The homozygous genotype of the MMP-3 gene in patients of the main group was verified in 42.1% of patients against 32.6% of cases in relatively healthy individuals (p=0.099).

Conclusion. We have proved the predominance of 6A allele and 6А6А genotype of the MMP-3 gene in the group of patients with DCM. It seems that it is homozygous 6A allele that causes a decrease in the activity of the transcription process and change in the level of stromelysin in arterial walls. This contributes to the activation of type 1 procollagenase, extracellular matrix deposition and cardiac muscle remodeling.

About the authors

Oxana O. Kuznetsova

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: nicoulina@mail.ru

Cand. Sci. (Med.)

Russian Federation

Svetlana Yu. Nikulina

Voino-Yasenetsky Krasnoyarsk State Medical University

Author for correspondence.
Email: nicoulina@mail.ru

D. Sci. (Med.)

Russian Federation

Anna A. Chernova

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: anechkachernova@yandex.ru

D. Sci. (Med.)

Russian Federation

Vladimir N. Maksimov

Voino-Yasenetsky Krasnoyarsk State Medical University; 2Institute of Internal and Preventive Medicine – a branch of the Federal Research Center Institute of Cytology and Genetics

Email: medik11@mail.ru

D. Sci. (Med.)

Russian Federation

References

  1. Elliott P, Andersson B, Arbustini E et al. Classification of the cardiomyopathies: a position statement from the European society of cardiology working group on myocardial and pericardial diseases. Eur Heart J 2008; 29 (2): 270–6. doi: 10.1093/eurheartj/ehm342
  2. Барт Б.Я., Беневская В.Ф. Дилатационная кардиомиопатия в практике терапевта и кардиолога (лекция). Терапевтический архив. 2004; 79 (1): 12–7.
  3. [Bart B.Y., Benevskaya V.F. Dilated cardiomyopathy in therapeutic and cardiological practice (lecture). Therapeutic Archive. 2004; 79 (1): 12–7 (in Russian).]
  4. Sugrue DD, Rodeheffer RJ, Codd MB et al. The clinical course of idiopathic dilated cardiomyopathy: A population-based study. Ann Intern Med 1992; 117 (2): 117–23. doi: 10.7326/0003-4819-117-2-117
  5. Startari U, Taylor MR, Sinagra G et al. Dilated cardiomyopathy: Etiology, clinical criteria for diagnosis and screening of the familial form. Ital Heart J Suppl 2002; 3 (4): 378–85.
  6. Medley TL, Kingwell BA, Gatzka CD et al. Matrix metalloproteinase-3 genotype contributes to age-related aortic stiffening through modulation of gene and protein expression. Circ Res 2003; 92 (11): 1254–61. doi: 10.1161/01.RES.0000076891.24317.CA
  7. Капелько В.И. Ремоделирование миокарда: роль матриксных металлопротеиназ. Кардиология. 2001; 41 (6): 49–55.
  8. [Kapelko V.I. Myocardial Remodeling: The Role of Matrix Metalloproteinases. Kardiologiia. 2001; 41 (6): 49–55 (in Russian).]
  9. Li J, Schwimmbeck PL, Tschope C et al. Collagen degradation in a murine myocarditis model: relevance of matrix metalloproteinase in association with inflammatory induction. Cardiovasc Res 2002; 56 (2): 235–47. doi: 10.1016/s0008-6363(02)00546-1
  10. Benjamin IJ. Matrix metalloproteinases: from biology to therapeutic strategies in cardiovascular disease. J Investig Med 2001; 49 (5): 381–97. doi: 10.2310/6650.2001.33783
  11. Creemers EE, Cleutjens JP, Smits JF et al. Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure? Circ Res 2001; 89 (3): 201–10. doi: 10.1161/hh1501.094396
  12. Hunt MJ, Aru GM, Hayden MR et al. Induction of oxidative stress and disintegrin metalloproteinase in human heart end-stage failure. Am J Physiol Lung Cell Mol Physiol 2002; 283 (2): L239. doi: 10.1152/ajplung.00001.2002
  13. Hojo Y, Ikeda U, Ueno S et al. Expression of matrix metalloproteinases in patients with acute myocardial infarction. Jpn Circ J 2001; 65 (2): 71–5. doi: 10.1253/jcj.65.71
  14. Mittal B, Mishra A, Srivastava A et al. Matrix metalloproteinases in coronary artery disease. Adv Clin Chem 2014; 64: 1–72. doi: 10.1016/b978-0-12-800263-6.00001-x
  15. Ye S. Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Cardiovasc Res 2006; 69 (3): 636–45. doi: 10.1016/j.cardiores.2005.07.015
  16. Гайковая Л.Б., Кухарчик Г.А., Нестерова Н.Н. и др. Современные лабораторные маркеры в определении прогноза при остром коронарном синдроме и мониторинге терапии. Вестник аритмологии. 2009; 58: 52–9.
  17. [Gaykovaya L.B., Kukharchik G.A., Nesterova N.N. et al. Modern laboratory markers in determining the prognosis for acute coronary syndrome and monitoring therapy. Journal of arrhythmology. 2009; 58: 52–9 (in Russian).]
  18. Humphries SE, Martin S, Cooper J et al. Interaction between smoking and the stromelysin-1 (ММР-3) gene 5A/6A promoter polymorphism and risk of coronary heart disease in healthy men. Ann Hum Genet 2002; 66 (5–6): 343–52.
  19. Xu X, Wang L, Xu C et al. Variations in matrix metalloproteinase-1, -3, and -9 genes and the risk of acute coronary syndrome and coronary artery disease in the Chinese Han population. Coron Artery Dis 2013; 24 (4): 259–65. doi: 10.1097/MCA.0b013e32835ea3af
  20. Dunleavey L, Beyzade S, Ye S. Rapid genotype analysis of the stromelysin gene 5A/6A polymorphism. Atherosclerosis 2000; 151 (2): 587–9. doi: 10.1016/S0021-9150(00)00443-3
  21. Tang LJ, Chen XF, Zhu M et al. Matrix metalloproteinase-1, -3, and -9 gene polymorphisms and the risk of idiopathic dilated cardiomyopathy in a Chinese Han population. Clin Biochem 2007; 40 (18): 1427–30. doi: 10.1016/j.clinbiochem.2007.09.013.

Copyright (c) 2020 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies