Faculty of Medicine

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Author: search.filters.author.Josifovska, SlavicaLanguage: search.filters.language.English

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    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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    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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    ADRENAL GLAND TLR EXPRESSION IN ApoE DEFICIENT HOMOZYGOUS (ApoE KO-/-) MICE WITH IMPAIRED THYROID FUNCTION
    (Macedonian Association of Anatomists and Morphologists, 2023-12)
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    Josifovska, Slavica
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    The main aim of our study was to investigate the expression of TLR receptors in the adrenal gland of ApoE knockout mice in context of ApoE deficiency as well as impaired thyroid function (hypo- and hyperthyroidism). The study was conducted on two following experimental animal groups: hypothyroid homozygous mice (ApoE KO-/-) treated with PTU; hyperthyroid homozygous mice (ApoE KO-/-) treated with L-thyroxine (T4) and two control groups: euthyroid homozygous mice (ApoE KO-/-) and euthyroid wild-type C57BL/6 mice (Bb). Determination of TLR gene expression in the adrenal gland was performed by RT-PCR reaction with semi-quantitative detection of populations of mRNA molecules transcribed from the TLR2, TLR4 and TLR9 genes in the adrenal gland in the treated experimental groups and the two untreated control groups. The results of our study are in support of the hypothesis that both conditions of impaired thyroid function produce TLR agonists that increase the expression of TLR in the adrenal gland (p<0,05). Also, in the untreated/control group of mice (ApoE KO-/-), an increased expression of TLR was found compared to the wild strain C57BL/6 mice (Bb) as a control group (p<0.001).
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    Association of the APOEgene polymorphism with diabetic nephropathy
    (Bioscientifica, 2020-08)
    Hasan, Taner
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    Josifovska, Slavica
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    Trajkovska, Ivana
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    Doneva, Daniela
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    Nedeska, Natasha
    The protein isoformes that are products of the Apolipoprotein E (APOB) gene polymorphism have partially altered biological activity and that may lead to greater susceptibility of the patientsto microvascular complications including Diabetic nephropathy (DN)in patients with the Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the association between the allele ε2, ε3, and ε4 of the APOE gene, as well as their combination, with the development of DN in patients with T2DM from the North Macedonia. The genotypic and allele frequency of the polymorphisms rs429358 and rs7412 in the APOE gene was determined in a group of patients with T2DM (with and without DN), and in the control group healthy subjects. The study is designed as a case-control genetic association study. The samples from 88 patients with T2DM were analyzed, including 57 patients with DN and 31 without DN and 26 healthy controls. The demographic, clinical and laboratory data were analyzed in addition to the genetic profiling of the patients. Genotyping of the APOE gene polymorphism resulted in determination of the patient’s genotype: ε2/ε2, ε3/ε3, ε4/ε4, ε2/ε3, ε2/ε4 or ε3/ε4, as well as of the alleles: ε2, ε3 or ε4. The results revealed a statistically significant association of the genotype ε2/ε3 (P = 0.016) and the allele ε2 (P = 0.020) with the occurrence of DN compared to the other genotypes and alleles. The presence of this genotype increases the chances of DN by 4,24 folds and the relative risk by 1,50 folds. In conclusion, the correlation of the APOEgene polymorphism and the development of the DN in patients with T2DM was confirmed indicating that there is a potential applicable value in the prognosis and treatment selection.
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    Association of the apoe gene polymorphism with diabetic nephropathy
    (SHMSHM - AAMD, 2019-02)
    Hasan, Taner
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    Pakovski, Kiril
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    Josifovska, Slavica
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    Baloski, Marjan
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    Nedeska Minova, Natasha
    The protein isoformes that are products of the Apolipoprotein E (APOB) gene polymorphism have partially altered biological activity and that may lead to greater susceptibility of the patients to microvascular complications including Diabetic nephropathy (DN) in patients with the Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the association between the allele Ԑ2, Ԑ3, and Ԑ4 of the APOE gene, as well as their combination, with the development of DN in patients with T2DM from the North Macedonia. The genotypic and allele frequency of the polymorphisms rs429358 and rs7412 in the APOE gene was determined in a group of patients with T2DM (with and without DN), and in the control group healthy subjects. The study is designed as a case-control genetic association study. The samples from 88 patients with T2DM were analyzed, including 57 patients with DN and 31 without DN and 26 healthy controls. The demographic, clinical and laboratory data were analyzed in addition to the genetic profiling of the patients. Genotyping of the APOE gene polymorphism resulted in determination of the patient’s genotype: Ԑ2/Ԑ2, Ԑ3/Ԑ3, Ԑ4/Ԑ4, Ԑ2/Ԑ3, Ԑ2/Ԑ4 or Ԑ3/Ԑ4, as well as of the alleles: Ԑ2, Ԑ3 or Ԑ4. The results revealed a statistically significant association of the genotype Ԑ2/Ԑ3 (p=0.016) and the allele Ԑ2 (p=0.020) with the occurrence of DN compared to the other genotypes and alleles. The presence of this genotype increases the chances of DN by 4,24 folds and the relative risk by 1,50 folds. In conclusion, the correlation of the APOE gene polymorphism and the development of the DN in patients with T2DM was confirmed indicating that there is a potential applicable value in the prognosis and treatment selection.
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    Association of the polymorphism rs3918242 of the matrix metalloproteinase-9 gene with coronary artery disease in a younger population
    (Macedonian Academy of Sciences and Arts, 2023-06)
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    Josifovska, Slavica
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    Coronary artery disease (CAD) is a complex disease resulting from the interaction of numerous so-called traditional risk factors and comorbid conditions on the one side (such as dyslipidemia, smoking, obesity, diabetes, hypertension) and genetic factors on the other. The evidence of a genetic contribution to the development of CAD, especially in the last 2 decades is consistent. It is important that a number of established gene polymorphisms in the younger CAD population are in the genes involved in the inflammatory response and tissue maintenance and remodeling processes. The aim of this study is to investigate the association of the rs3918242 polymorphism of the matrix metalloproteinase 9 (MMP9) gene with the coronary artery disease in the younger population. In this observational genetic-association study of cases and controls, the demographic, clinical, laboratory and genetic data of the younger population in a group of selected 70 CAD patients aged up to 45 years were analyzed, of which 35 patients have negative and 35 have positive coronary angiography finding, and 43 are men and 27 are women. The analysis of the genotypic and allelic frequency determined an association of the polymorphism and the occurrence of the positive coronary angiographic findings in the population of patients under the age of 45. The carriers of the heterozygous genotype CT have almost 5 times higher probability of having a positive coronary angiography finding compared to the carriers of the reference homozygous genotype CC (p=0.012). Thus, this parameter could be used for clinical risk assessment for the development of CAD.