ASSOCIATION OF THE RS1799750 MATRIX METALLOPROTEINASE-1 GENE POLYMORPHISM AND CORONARY ARTERY DISEASE IN YOUNG MACEDONIAN POPULATION
Abstract
Coronary artery disease (CAD) is very complex disease arising from close interaction of many risk-factors as well as presence of many comorbidities. Pathophysiology mechanisms may be different and encompass endothelial dysfunction, impaired lipid metabolism, chronic inflammation, thrombosis, and mechanisms associated with tissue maintenance and remodeling. In this research we aim to investigate the association between rs1799750 (-1607 1G/2G) matrix metalloproteinase – 1 (MMP-1) gene polymorphism and CAD in young Macedonian population. This is an observational, genetic-association study of cases and controls including 57 participants divided into two groups. The first is the group with positive coronary angiography (CA) finding (n=34) and the second is the group with negative CA finding (controls, n=34 participants). All of them underwent molecular and genetic analyses after performed CA. Complete comparison of the frequencies of genotypes and alleles of the rs1799750 MMP-1 gene polymorphism was used for statistical analysis. Calculations were performed using Chi-square test (x2-test) and Fisher's exact test for analysis of the genotype and allele frequencies of the gene polymorphism using five different models. The Cochran-Armitage trend test was used to analyse the allelic frequencies with the allelic and additive model. The statistical analyses were performed using XLSTAT 2016, GenAIEx 6.5 and Microsoft Excel 2016 software. According to the genotypic model, carriers of the heterozygous 1G/2G genotype have 2,8 times higher probability whereas carriers of the 2G/2G genotype have 7,389 times higher probability for development of CAD in comparison to the reference carriers of 1G/1G, respectively (p<0,05). The dominant model has also confirmed that genotype carriers with at least one 2G allele have 4,521 times higher probability for CAD in comparison to homozygous 1G/1G genotype carriers (p<0,05). According to the recessive model, participants with homozygous 2G/2G genotype have statistically significant 3,589 times higher probability for CAD in comparison to participants with at least one 1G allele (p<0,05). Allelic model also proved that carriers of the 2G allele have 3 times higher chances for development of CAD than the carriers of the 1G allele (p<0,05). The last, additive model, confirmed that the risk increases with the number of present 2G allele. Results from our study clearly show that there is statistically significant genetic association of the rs1799750 MMP-1 gene polymorphism with significant CAD in young Macedonian population. More specifically, presence of genotype 2G/2G as well as allele 2G leads to statistically significant increase of the probability for CAD.
Key words: CAD, MMP-1, gene polymorphism, rs1799750.
References
2. Malinowsky D. et al. Genetic Risk Factors Related to Coronary Artery Disease and Role of Transforming Factor Beta 1 Polymorphisms. Genes 2023, 14, 1425. https://doi.org/10.3390/genes14071425
3. Bräuninger H. et al. Matrix metalloproteinases in coronary artery disease and myocardial infarction. Basic Research in Cardiology (2023) 118:18. https://doi.org/10.1007/s00395-023-00987-2
4. Kapoor C. et al. Seesaw of matrix metalloproteinases (MMPs). J Can Res Ther 2016; 12: 28-35. DOI: 10.4103/0973-1482.157337
5. Niu W., Qi Y. Matrix Metalloproteinase Family Gene Polymorphisms and Risk for Coronary Artery Disease: Systemic Review and Meta-Analysis. Heart 2012; 98:1483e1491. doi:10.1136/heartjnl-2012-302085
6. Ikeda U, Shimada K. Matrix Metalloproteinase and Coronary Artery Diseases. Clin Cardiol 2003; 26: 55-59
7. Pawlik A. et al. MMP1 and MMP3 Gene Polymorphisms in Patients with Acute Coronary Syndromes. IUBMB Life 2017; Vol 69, No 11, p.850-855. DOI 10.1002/iub.1684
8. Kondapalli MS et al. MMP-1 circulating levels and promoter polymorphism in risk prediction of coronary artery disease in asymptomatic first-degree relatives. Gene 595 (2016) 115–120. http://dx.doi.org/10.1016/j.gene.2016.09.041
9. Nishizawa R. et al. The 2G allele of promoter region of matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma. BMC Cancer. 2007 Oct 5;7:187. doi: 10.1186/1471-2407-7-187
10. Dalepiane VLN et al. Matrix Metalloproteinase Gene Polymorphisms in Patients with Coronary Artery Disease. Genetics and Molecular Biology, 30, 3, 505-510 (2007)
11. Qintao C., Yan L., Changhong D., Xiaoliang G., Xiaochen L. Genetic Polymorphism of Matrix Metalloproteinase-1 and Coronary Artery Disease Susceptibility: A Case-Control Study in a Han Chinese Population. GENETIC TESTING AND MOLECULAR BIOMARKERS, Vol. 18, No 12, 2014, p.826-831. DOI: 10.1089/gtmb.2014.0222
12. Sakowicz A., Fendler W., Lelonek M., Pietrucha T. Genetic variability and the risk ofmyocardial infarction in Poles under 45 years of age. Arch Med Sci 2010; 6, 2: 160-167. DOI: 10.5114/aoms.2010.13887
13. Ghaffarzadeh A., Bagheri M., Khadem-Vatani K., Abdi Rad I. Association of MMP-1 (rs1799750)-1607 2G/2G and MMP-3 (rs3025058)-1612 6A/6A Genotypes with Coronary Artery Disease Risk Among Iranian Turks. J Cardiovasc Pharmacol 2019;74:420–425.
