Faculty of Medicine

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Association of ACEI//D Gene Polymorphism with Diabetic Nephropathy.
(Scientific association of endocrinologists and diabetologists of Macedonia, 2018-05)
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Trajkovska, Ivana
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Doneva, Daniela
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Nedevska Minova, Natasha
Diabetic nephropathy (DN) is considered as a major microvascular complication of type 2 diabetes mellitus (T2DM) and is the leading cause of end-stage renal disease. Genetic susceptibility is a significant risk factor for DN development including the polymorphisms in ACE gene. The aim of this study is to investigate the association of ACE gene I/D polymorphism with DN in T2DM patients. In this prospective, observational, genetic association, case-control study, a demographic, clinical and laboratory data are analyzed from preliminary selected group of 35 patients with T2DM, of which 17 are with DN and 18 without DN. The duration of T2DM is similar to both subgroups. As controls, blood samples from 30 healthy blood donors and volunteers are being collected. Genetic analyses revealed statistically significant (p=0.029) association of genotypes D/D and I/D with occurrence of nephropathy, regarding the homozygous I/I genotype. Carriers of D/D and I/D genotypes has 7.134 folds higher odds and 2.148 folds higher relative risk for developing nephropathy than the carriers of I/I genotype among the patients with T2DM. Although the data and samples from only 35 patients are calculated, preliminary analyses indicates that there is a potential applicable predictive value of determination of this polymorphism during the clinical follow-up, treatment selection and prognosis of diabetic nephropathy.
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Empty Sella Syndrome with Profound Hypopituitarism
(Scientific association of endocrinologists and diabetologists of Macedonia, 2018-05)
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Hasan, Taner
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Doneva, Daniela
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Nedeska Minova, Natasha
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Trajkovska, Ivana
Empty sella (ES) is characterized by herniation of subarachnoid space within the sella caused by various etiopathogenetic mechanisms. Although ES can be presented as benign and asymptomatic condition, it can be also associated with pituitary dysfunction, opthalmologic and neurological abnormalities. Case report: We describe a case of empty sella with profound hypopituitarism. A 36-year-old man was refered to our hospital for evaluation of his obesity. He had complaints of decreased libido, anejaculation, depressive mood and lack of energy for several years. On examination he had body mass index 34kg/m2, waist circumference 108 cm and normal blood pressure. His medical history was unremarkable except for previous head injury. The hormone analysis showed TSH l 9.95 uIU/ml (0.4-4.0), free T4 0.64ng/dl (0.90-1.80), free T3 2.14 pg/ml (1.80-4.20), LH 0.710 mIU/ml(0.80-7.60), FSH 3,25mIU/ml (0.70-11.1), GH 0.05ng/ml (<5ng/ml), prolactin 25ng/ml (2-29) cortisol 3.45ug/dl (5-25) and ACTH 14.3pg/ml (5-48). Other laboratory investigation were significant for hyperinsulinemia, 41 uIU/ml (2-29.1) and atherogenic lipid profile. Furthermore the patient had severe vitamin D deficiency 18.6 nmol/L (75-250). Magnetic resonance imaging of hypotalamic-pituitary area revealed invagination of subarachnoid space to sella, narrow glandular tissue on the left side and pituitary microadneoma of 6 mm within it. Ophtalmological and visual filed examination were insignificant. Replacement hormonal therapy was initiated and patient clinically improved. Conclusion: in our patient ES might be a consequence of previous brain injury. ES syndrome is characterized by variable clinical manifestations. Therefore, patients with ES should be subjected to endocrinological, neurological and ophthalmological evaluation.
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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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Graft-versus-host disease in patients treated with allogenic hematopoetic cell transplantation: experience from North Macedonia
(VM Media SP. zo.o VM Group SK, 2021-10-28)
Mickovski, Ivana
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Hasan, Taner
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Nedeska Minova, Natasha
Introduction: Graft-versus-host disease (GvHD) is the major complication arising after allogeneic hematopoietic cell transplantation (allo-HCT). It can be presented as acute and/or chronic GvHD. The purpose of this study was describe the incidence of acute and chronic GvHD in patients treated with allo-HCT. Materials and methods: This study was designed as a retrospective study, which included 65 patients treated with allogeneic transplantation from human leukocyte antigen identical donor at University Clinic of Hematology in Skopje, North Macedonia. Results: Acute GvHD (aGvHD) was observed in 28 patients, with the most common localization on the skin (75%). Post-transplant phase had significant effect on the frequency of skin aGvHD (p =0.038). Also statistically significant difference was confirmed between patients with and without acute skin GvHD in terms of conditioning regimen (p =0.034). Chronic GvHD (cGvHD) was diagnosed in 10 patients, mostly progressing from the previous acute GvHD (9.23%). Post-transplant phase had also significant effect on the frequency of skin cGvHD (p =0.018). Patients with higher European Society for Blood and Marrow Transplantation risk score had significantly more frequent skin cGvHD than the others. Conclusions: Acute and chronic GvHD were one of the main causes of morbidity and mortality of patients after aloo-HCT. GvHD remains a major risk for patients with allo-HCT regardless of diagnosis and type of transplantation.

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