Faculty of Medicine

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    Item type:Publication,
    Association of the rs1799750 Matrix Metalloproteinase-1 Gene Polymorphism and Coronary Artery Disease in Young Macedonian Population
    (Macedonian Association of Anatomists and Morphologists, 2024-10-23)
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    Stankovic, Svetlana
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    Pakovski, Kiril
    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.
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    Item type:Publication,
    THE ROLE OF MATRIX METALLOPROTEINASE-1 AND ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISMS IN DEVELOPMENT OF CORONARY ARTERY DISEASE
    (Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2024-07)
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    Josifovska, Slavica
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    Pakovski, Kiril
    Coronary artery disease (CAD) is one of the major causes of morbidity and mortality worldwide. The main pathophysiological processes involved in the development of CAD include impaired lipid metabolism, coagulation and chronic inflammation of the coronary vessel wall. There are many well-known traditional or conventional risk factors that may contribute to development of CAD like smoking cigarettes, lack of physical activity, diabetes, obesity, arterial hypertension, dyslipidemia (hypercholesterolemia), psychosocial stress etc. Nevertheless, over the last two decades there has been a significant progress in the field of genetic research and enlightening of the genetic basis of development of CAD. Certain genetic polymorphisms have been found to be linked not only to lipid metabolism and coagulation but also to inflammation and response, tissue maintenance, remodeling and degradation of the extracellular matrix. In this review article we discuss some of the most frequently studied gene polymorphisms in the development of CAD – matrix metalloproteinase-1 (MMP-1) and endothelial nitric oxide synthase (eNOS) gene polymorphisms.
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    Item type:Publication,
    Association of Killer Cell Immunoglobulin-Like Receptor Genes with Pandemic Influenza A (H1N1)pdm09 Infection in Critically Ill Macedonian Patients
    (Scientific Foundation SPIROSKI, 2012)
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    Eli Djulejic
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    Bisera Jefremovska
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    Haris Babacic
    Background: Infection by the pandemic influenza A (H1N1)pdm09 virus results in significant pathology disease in many cases in different populations worldwide. The natural killer (NK) cells are among the major effectors important in early innate immune responses to viral infections, interacting with host cells through their activating or inhibiting receptors. Aim: The aim of this study was to analyze Killer Ig-Like Receptor (KIR) gene polymorphisms in critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection. Material and Methods: The studied sample consists of 63 critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection. The population genetics analysis package, Arlequin, was used for analysis of the data. Results: We found that all 16 KIR genes were observed in the studied individuals and framework genes (KIR3DL3, KIR3DP1, KIR2DL4, and KIR3DL2) were present in all individuals. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a wide range of linkage disequilibrium. Comparison of KIR gene frequencies between critically ill H1N1/09 Macedonian patients and healthy subjects reveals statistically significant difference for frequency of KIR2DL1 (F=1 in the patients group, and 0.94 in the control group, p=0.045). Conclusion: We did not found any significant association of all 16 KIR genes or KIR genotypes with critically ill (H1N1)pdm09 Macedonian patients, except for the KIR2DL1.