Emina Kiseljaković

Is γ-glutamyl transferase activity a potential marker of left ventricular function during early postmyocardial infarction period?

AIM γ-glutamyl transferase (GGT) is an independent prognostic marker for cardiac death and reinfarction in patients with coronary artery disease, but its clinical significance during early postmyocardial infarction period is unclear. PATIENTS & METHODS This short-term prospective study included 40 patients with acute myocardial infarction (AMI) in whom we determined GGT activity, lipids, uric acid, homocysteine (Hcy), high sensitivity C-reactive protein (hsCRP) and left ventricular (LV) function on admission and on day 5 following AMI. RESULTS In AMI patients on admission, logGGT was associated with logHcy (r = 0.36), uric acid (r = 0.48) and CK-MB activity (r = -0.41). Uric acid remained an independent determinant of serum GGT activity on admission. Significant increase in GGT activity (77.7%) was observed following AMI. On day 5 serum logGGT was significantly associated with LV relative wall thickness (r = -0.37), LV end-diastolic diameter (r = 0.41) and LV fractional shortening (r = -0.36). In addition, a significant positive correlation was found between serum logGGT and loghsCRP (r = 0.41) and logHcy values (r = 0.395), but only LV end-diastolic diameter remained independently associated with serum GGT activity on day 5 following AMI. CONCLUSION GGT is associated with oxidative/inflammatory markers and LV diastolic diameter suggesting its potential role in predicting LV dilatation and dysfunction during the early postmyocardial infarction period.

Renalase Gene rs2576178 Polymorphism in Hemodialysis Patients: Study in Bosnia and Herzegovina -

Introduction: Renalase is a protein secreted in kidneys and considered as a blood pressure modulator. High rates of hypertension and its regulation in patients on hemodialysis demands search for potential cause and treatment. The aim of this study was to determine the genotype and allele frequencies of renalase gene rs2576178 polymorphism in population from Bosnia and Herzegovina. Also, the objective of present study was to find the possible association between renalase gene rs2576178 polymorphism and hypertension in patients on hemodialysis. Material and Methods: The genotype of renalase gene rs2576178 polymorphism was determined in 137 participants (100 patients on hemodialysis and 37 controls), using polymerase chain reaction (PCR) and subsequent cleavage with MspI restriction endonuclease. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium using a Chi-squared test. The value of P<0.05 was considered as statistically significant. Results: Comparison of genotype distribution and allele frequency in participants on hemodialysis with and without hypertension, and healthy control showed no statistical difference. Conclusion: The results of the study suggest that renalase gene rs2576178 polymorphism is not a factor that influences blood pressure in patients on hemodialysis.

Prevalence of genetic prothrombotic risk factors: 1691G > A FV, 20210G > A PT and 677C > T MTHFR mutations in the Bosnian population

Abstract Background: Venous thrombosis (VT) affects 1–2 out of 103 individuals each year. Mutations of 1691G > A FV gene, 20210G > A PT gene and 677C > T gene MTHFR are common in Europe and increase the risk of venous thrombosis. To the authors’ knowledge, this is the first report on the prevalence of these mutations in the general population of Bosnia and Herzegovina. Aim: The aim of this study was to simultaneously analyse main VT associated polymorphisms and compare the results with those published for other European populations. Data sources: Electronic databases including Medline and Embase were searched from 1995 to December 2013. Subjects and methods: The subjects of the study consisted of 100 unrelated healthy people from Bosnia and Herzegovina (82 female and 18 male). The mean age of the cohort was 58.8 (±10.7) years. PCR-RFLP was used for measurement of allele frequencies. Results: All three SNPs were found to be polymorphic, with allele frequencies of 6.0%, 6.0% and 37.5% for 1691A FV, 20210A PT and 677T MTHFR, respectively. Conclusion: Further studies on larger cohorts with an adequate female-to-male ratio are necessary to confirm a high prevalence of hereditary thrombophilia in the Bosnian population.

Serum Uric Acid Could Differentiate Acute Myocardial Infarction and Unstable Angina Pectoris in Hyperuricemic Acute Coronary Syndrome Patients

Introduction: Serum uric acid (SUA) is the final product of purine metabolism in humans. Aim: The present study aimed to identify a potential association between serum UA and cardiac troponin I (cTnI) levels and to find out whether uric acid could differentiate patients presenting with the acute myocardial infarction (AMI) and unstable angina pectoris (UAP) in hyperuricemic and normouricemic acute coronary syndrome (ACS) patients. Methods: Eighty ACS patients, aged 50-83 years, were enrolled in the study, 40 of them presenting with AMI and 40 with UAP. Frequency of patients with serum uric level over threshold for hyperuricemia was investigated and two groups of patients were formed such as hyperuricemic and normouricemic groups (A and B groups, respectively) independently of type of ACS. Those groups of patients were also subjected to cTnI measurement. Results: Levels of SUA are associated with the type of ACS in the hyperuricemic ACS patients (AMI versus UAP, 499(458-590), 425(400-447) mmol/L, p=0.007, respectively). Uric acid correlated significantly with cTnI, moderate positively in the group A (rho=0.358, p=0.038) and moderate negatively in the group B (r=-0.309, p=0.037) of ACS patients. Multiple logistic regression analysis revealed that cTnI and age were independently associated with the SUA levels in the group A of ACS patients. Conclusions: Serum uric acid differentiates AIM and UAP patients in hyperuricemic group of acute coronary syndrome. Therefore it can be used as nonspecific parameter for evaluation of the myocardial lesion extent only in hyperuricemic ACS patients. This is supported by finding that cTnI along with age predicts SUA level in hyperuricemic ACS patients.

Cytogenetic Abnormalities Found in Patients with Reproductive Problems

Introduction One of the important causes of male infertility is aberration at the chromosomes. Aim The main purpose of this study was to determine the frequency and types of chromosomal aberration in infertile/sterile men whose samples were analyzed in the Center for Cytogenetics of Faculty of Medicine University of Sarajevo in the last four years. Methods A total of 353 infertile/sterile men, between the ages of 22-55 years, referred for cytogenetic analysis to the Center for Genetics of Faculty of Medicine during the period 2013-2016. Karyotyping was performed on peripheral blood lymphocytes by using the Giemsa trypsin banding (GTG) technique. Results The structural and numerical chromosomal aberration in infertility/ sterility of men found with the incidence of 6% (20/353). Out of the 20 patients with abnormal cytogenetic diagnosis, structural chromosome abnormalities were observed in 17 (85%) patients and 3 (15%) with numerical aberrations. The type of aberrations mostly found were Robertsonian and reciprocal translocations (35%, 35%, respectively). Conclusions The incidence of chromosomal abnormalities in infertile/sterile males suggests that the cytogenetics analysis is an important in male infertility, especially if it will be used for the purpose of assisted reproduction techniques.

Bosnian study of APOE distribution (BOSAD): a comparison with other European populations

Abstract Background: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. Aim: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations. Subjects and Methods: Overall, 170 unrelated Bosnian subjects (108 female and 62 male), aged 53.0 (±5.0) years were included in this study. Genotypes were determined by real-time PCR. Results: In our group the prevalence of heterozygotes E2/E3, E2/E4 and E3/E4 was 20.6%, 3.5% and 12.9%, respectively, while the prevalence of homozygotes E2/E2, E3/E3, E4/E4 was 0.6%, 61.2% and 1.2%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 12.6%, 78.0% and 9.4%, respectively. Conclusions: In studied European populations we observed a linear, gradually increasing trend in the frequency of ε4 allele from South to North (Pearson’s test 0,7656, p value <0.00001), and the Bosnian population fits into this pattern perfectly.

Dilemma: Correlation Between Serum Level of Hepcidin and IL-6 in Anemic Myeloma Patients -

Introduction: Anemia occurs in 60% to 80 % of patients with newly diagnosed myeloma multiplex (MM). The cause of anemia in MM is probably multi factorial and involved among the others hepcidin and some cytokines, especially interleukine-6. Anemia in MM is one of the risk factor used in Durie-Salmon classification for staging and prognostic score. Treatment options are set according to this score with most significant impact on survival. Aim: To estimate baseline level of serum hepcidin, IL-6 and iron metabolism markers in anemic MM patients, possible role of hepcidin and its interaction with IL-6. Methods: 27 patients with newly diagnosed MM were enrolled in this observational, prospective study and age, gender matched 60 healthy controls. Erythrocyte count, hemoglobin, serum hepcidin, interleukin-6, iron, ferritin and transferrin were measured. Results: Anemia was diagnosed in 70% of MM patients. Serum hepcidin was significantly higher in MM group (55.5 ng/mL) than in control 5.9 ng/mL (p=0000). In myeloma patients serum IL-6 was 3.59 pg/mL, anemic 3.80 pg/mL, non-anemic 0.33 pg/mL, without significant difference. It was not found significant correlation between hepcidin and IL-6 in anemic myeloma patients. Conclusion: High level of hepcidin probably causes anemia in MM but its high expression is not due only to IL-6.

Positive correlation between uric acid and C-reactive protein serum level in healthy individuals and patients with acute coronary syndromes.

AIM To assess serum levels and correlation between uric acid (UA) and C-reactive protein (CRP) in acute coronary syndrome (ACS) and apparently healthy individuals. METHODS The cross-sectional study included 116 examinees of age 44 to 83 years, distributed in two groups: 80 ACS patients including 40 with acute myocardial infarction (AMI), and 40 with unstable angina pectoris (UAP), and 36 apparently healthy (control group) individuals. Patients with ACS were hospitalized at the Cardiology Clinic, Clinical Centre Sarajevo in the period October- December 2012. Laboratory analyses were conducted by standard methods. The accepted statistical significance level was p<0.05. RESULTS Serum levels of CRP and UA were higher in patients with ACS as compared to control group (p<0.01). The median serum UA was insignificantly lower, and CRP was significantly higher in patients with AMI compared to UAP (p=0.118 and p=0.001, respectively). CRP and UA correlated positively in both ACS and control groups (rho=0.246; p=0.028 and rho=0.374; p=0.027). A positive correlation between serum CRP and UA was noted in patients with AMI, but negative in patients with UAP (p>0.05). CONCLUSION The correlation between CRP and UA in the patients with ACS indicates the association of oxidative stress and inflammation intensity in damaged cardiomyocytes. Correlation between UA and CRP in apparently healthy individuals indicates a possible role of UA as a marker of low-grade inflammation and its potential in risk assessment in cardiovascular diseases.

Association of Parental Age and the Type of Down Syndrome on the Territory of Bosnia and Herzegovina

Background: Advanced paternal and/or maternal age is a classic risk factor for Down syndrome. The aim of the study was to investigate the frequency of Down syndrome types in children and its association with maternal and paternal age in Bosnia and Herzegovina. Subjects and Methods: The cross sectional, observational study included 127 children, 49 girls and 78 boys, aged 1-180 months suspected to have Down syndrome, admitted to the Centre for Genetics, Faculty of Medicine University of Sarajevo, for cytogenetic analysis and differential diagnosis of Down syndrome during the period from January 2010 to May 2015. Standard method of 72 hours cultivation of peripheral blood lymphocytes has been applied. The accepted level of statistical significance was p<0.05. Study Results: The most common type of Down syndrome was standard trisomy (86.6%), comparing to translocation and mosaicism (7.1%; 6.3%, respectively). The highest frequency of Down syndrome cases was in mother and father’s group from 30-39 years old (57; 57 children, respectively) compared to mother and father’s groups with younger than 30 (44; 29, respectively) and 40 and older (26; 41, respectively). The significant difference was found in maternal age between translocation and mosaicism groups (p=0.036). Difference between parental years and type of Down syndrome was significant when Standard trisomy 21 and translocation (p=0.045), as well as mosaicism and translocation (p=0.036), were compared. Conclusion: The most common type of Down syndrome was standard trisomy 21, with highest occurrence in parents from 30 to 39 years old. Parents were the youngest in translocation group. Obtained results suggest that multidisciplinary approach to identifying the trigger for trisomy appearance and the influence of maternal age is required.