Associations of the rs1132896 polymorphism of the matrix metalloproteinase type 2 gene with the development of acute cerebrovascular accident: prospective case–control study

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Abstract
BACKGROUND: The study focused on the identification of new genetic predictors in the Russian population, particularly associations of the rs1132896 polymorphism of the matrix metalloproteinase type 2 gene (MMP-2) with the development of acute cerebrovascular accident (ACVA). OBJECTIVE: To investigate the relationship of rs1132896 gene MMP-2 polymorphisms with ACVA development. MATERIALS AND METHODS: The prospective, case–control study enrolled 318 patients with stroke (main group) and 323 controls (control group). The age of the patients in the main group ranged from 32 to 69 [57.0; 51.0–62.0] years. In the control group, the age of the patients ranged from 37 to 68 [55.0; 51.0–62.0] years, which was comparable to that of the main group. Sexual dimorphism was as follows: 191 men (age [56.5; 51.0–62.0]) and 127 women (age [57.0; 51.0–62.0]). The sex composition in the control group corresponded to that in the main group: 214 men (age [55.0; 51.0–62.0]) and 109 women (age [55.0; 51.0–62.0]). The main group underwent clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, duplex ultrasound scanning of the extracranial brachiocephalic arteries, 24-h monitoring of blood pressure and heart rate, and analysis of the blood coagulation system. Molecular genetic research was conducted at a branch of the Institute of Cytology and Genetics of the Siberian Branch of RAS (Novosibirsk). All patients provided written informed consent to participate voluntarily in the study. The duration of the study was 3 years, starting in 2019. The primary study endpoint was a diagnosis of stroke, verification of concomitant cardiovascular pathology, and risk factors for stroke development. Statistical processing of the results was performed using SPSS Statistics v. 22 (IBM Corp., USA) and MedCalc 22.006 (Microsoft, USA). When comparing extended variables, the Mann–Whitney U-test was used. Discrete values were compared using Pearson’s χ2 test. RESULTS: When analyzing statistical significance, a predominance of the homozygous CC genotype was recorded in the group of male patients with stroke: n=24 (12.6%) vs n=20 (9.3%; p=0.0324). In addition, in the group of women, a statistically significant predominance of the heterozygous CG genotype was noted in women with stroke: n=67 (52.8%) vs n=42 (38.5%; p=0.0420). CONCLUSION: The homozygous CC genotype in men and the heterozygous CG genotype in women may be genetic predictors of the development of ACVA. The study of genetic factors in the development of ACVA is necessary to create a personalized approach to patient management at the outpatient and inpatient stages of medical care.

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