Results of the association study of the type 3 matrix metalloproteinase gene - 1171 5A/6A (rs35068180) and dilated cardiomyopathy
Authors: Nikulina S , Kuznecova O , Chernova A 
Published: April 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Background
Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in &gt;30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype.

Research objective
The purpose of the present study was to determine the association between matrix metalloproteinase -3 (MMP-3) gene polymorphism - 1171 5A/6A (rs35068180) with myocardial dilation of ischemic and idiopathic origin.

Materials and methods
We studied 221 patients with with myocardial dilation of ischemic and idiopathic origin. Their average age was 55.30 ± 9.69 years. The group of patients with with myocardial dilation of ischemic origin consisted of 111 people, including 99 men (89.2%) and 12 women (10.8%). The average age of the subjects with myocardial dilation of ischemic origin 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 myocardial dilation of idiopathic origin were included in the study. There were 100 male patients (91.5%) and 10 female patients (8.5%). The average age of the studied patients with myocardial dilation of idiopathic origin was 58.68 ± 8.38 years, in men it was 58.29 ± 8.46 years, in women - 62.90 ± 6.29 years. The control group of subjects (121 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. All patients underwent PCR to determine - 1171 5A/6A (rs35068180) polymorphism of the MMR gene.

Results
Patients with cardiomyopathies in the general group, regardless of the etiology of the disease, demonstrated statistically significant differences compared with the control group subjects. 6A allele (65.8% versus 59.3%, p = 0.044) and 6A / 6A genotype (42.1% versus 32.6%, p = 0.099) were significantly more frequent in patients with cardiomyopathies than in the control group. In addition, despite various etiological factors, the participation of the MMP-3 protein in the pathogenesis of these cardiomyopathies, probably, has a general tendency.

Conclusion
We have proved the predominance of the MMP-3 gene A allele in the cardiomyopathies group without taking into account the etiological factors of the disease development. In connection with a decrease in the activity of the transcription process in case of homozygous 6A allele, the level of stromelysin in arterial walls also decreases. This contributes to the activation of type 1 procollagenase, extracellular matrix deposition and cardiac muscle remodeling.