Publications by authors named "Damir Marjanovic"

71 Publications

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort.

J Neural Transm (Vienna) 2021 Nov 27. Epub 2021 Nov 27.

Department of Psychiatry, University Clinical Center, Sarajevo, Bosnia and Herzegovina.

Objectives: Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables.

Methods: Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables.

Results: The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD.

Conclusions: The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.
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http://dx.doi.org/10.1007/s00702-021-02446-5DOI Listing
November 2021

Prevalence of rare F5 variants in general population from Bosnia and Herzegovina.

Mol Biol Rep 2021 Jun 2;48(6):5181-5186. Epub 2021 Jul 2.

St. Catherine Specialty Hospital, Zagreb and Zabok, Croatia.

Human gene F5, encoding coagulation factor V, was previously reported to be highly polymorphic. Apart from FV Leiden, several other rare variants have been detected in clinical practice and associated with thrombotic events, especially in cases when patient's phenotype and FV Leiden genotype were not in agreement. In this study, the prevalence of 17 rare F5 variants has been studied on a sample of 130 healthy adult individuals from the general Bosnian-Herzegovinian population. DNA was isolated from buccal swab samples, while genotyping was performed using MALDI-TOF MS method. The results have shown that Asp2194Gly and Met2120Thr are polymorphic in the study population with minor allele frequencies of 0.077 and 0.073, respectively. Additionally, these two variants were mutually exclusive with FV Leiden and none of them was positively associated with participants' family history of cardiovascular or cerebrovascular diseases. While the obtained results are in agreement with previously reported data for the general Caucasian populations, it is worth noting that only two rare F5 variants were detected in the study population, albeit at considerable frequencies. Still, scientific information on rare F5 variants is rather scarce and further studies aiming to assess functional importance of these variants, as well as their role as prothrombotic factors are necessary.
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http://dx.doi.org/10.1007/s11033-021-06519-2DOI Listing
June 2021

Haplogroup Prediction Using Y-Chromosomal Short Tandem Repeats in the General Population of Bosnia and Herzegovina.

Front Genet 2021 11;12:671467. Epub 2021 Jun 11.

Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina.

Human Y-chromosomal haplogroups are an important tool used in population genetics and forensic genetics. A conventional method used for Y haplogroup assignment is based on a set of Y-single nucleotide polymorphism (SNP) markers deployed, which exploits the low mutation rate nature of these markers. Y chromosome haplogroups can be successfully predicted from Y-short tandem repeat (STR) markers using different software packages, and this method gained much attention recently due to its labor-, time-, and cost-effectiveness. The present study was based on the analysis of a total of 480 adult male buccal swab samples collected from different regions of Bosnia and Herzegovina. Y haplogroup prediction was performed using Whit Athey's Haplogroup Predictor, based on haplotype data on 23 Y-STR markers contained within the PowerPlex® Y23 kit. The results revealed the existence of 14 different haplogroups, with I2a, R1a, and E1b1b being the most prevalent with frequencies of 43.13, 14.79, and 14.58%, respectively. Compared to the previously published studies on Bosnian-Herzegovinian population based on Y-SNP and Y-STR data, this study represents an upgrade of molecular genetic data with a significantly larger number of samples, thus offering more accurate results and higher probability of detecting rare haplogroups.
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http://dx.doi.org/10.3389/fgene.2021.671467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226213PMC
June 2021

Serological testing for SARS-CoV-2 in Bosnia and Herzegovina: first report.

Arch Med Sci 2021 18;17(3):823-826. Epub 2021 Mar 18.

Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina.

Introduction: Serological detection of SARS-CoV-2-specific immunoglobulins G (IgG) and M (IgM) antibodies is becoming increasingly important in the management of the COVID-19 pandemic.

Methods: We report the first results of COVID-19 serological testing in Bosnia and Herzegovina on 2841 samples collected and analysed in 2 medical institutions in Sarajevo. Antibody detection was performed using commercially available kits.

Results: In the first cohort, 43 IgM-positive/IgG-negative and 16 IgM-positive/IgG-positive individuals were detected, corresponding to 3.41% of participants having developed antibodies. In the second cohort, 4.28% participants were found to be IgM-negative/IgG-positive.

Conclusions: Our results suggest the need for population-wide serological surveying in Bosnia and Herzegovina.
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http://dx.doi.org/10.5114/aoms/134143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130482PMC
March 2021

Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches.

Bosn J Basic Med Sci 2021 Aug 1;21(4):484-487. Epub 2021 Aug 1.

The Academy of Science and Arts of Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina.

This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing severe acute respiratory syndrome coronavirus 2 epidemic. Whole genome sequence of four samples from coronavirus disease 2019 (COVID-19) outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, and England). The constructed phylogenetic tree indicates possible multiple independent introduction events. The data presented contribute to a better understanding of COVID-19 in the current reemergence of the disease.
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http://dx.doi.org/10.17305/bjbms.2020.5381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292857PMC
August 2021

Distribution of the Allele in the Bosnian-Herzegovinian Population and its Possible Role in the Regional Epidemiological Picture of COVID-19.

Genet Test Mol Biomarkers 2021 Jan 28;25(1):55-58. Epub 2020 Dec 28.

Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina.

The human angiotensin I converting enzyme 1 ( gene insertion/deletion (I/D) polymorphism is classified based on the presence or absence of a 287 bp sequence. The allele is associated with higher concentrations in tissues. Previous research has shown that susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is primarily determined by the affinity between the viral receptor-binding domain and the host human receptor angiotensin-converting enzyme 2 (hACE2) receptor. In the human genome, is identified as a homolog to . The purpose of this study was to characterize the allele distribution in Bosnia and Herzegovina (B&H), so as to compare it to population data from other European countries and to investigate the potential correlation between allele frequencies and coronavirus disease 2019 (COVID-19) epidemiological findings in selected European populations. The allele frequencies in 18 selected European populations were analyzed and compared with COVID-19 prevalence, mortality, and severity using multivariate linear regression analysis. The allele distribution within the B&H population was similar to its distribution in other European populations. Regression analysis showed no significant correlation between the allele frequency and the incidence of infections between the examined populations, nor with the rates of fatality and severe cases. There is no clear statistical evidence that the allele is associated with increased or decreased COVID-19 incidence, mortality, and case severity within the investigated populations.
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http://dx.doi.org/10.1089/gtmb.2020.0207DOI Listing
January 2021

The Genomic Impact of European Colonization of the Americas.

Curr Biol 2019 12 14;29(23):3974-3986.e4. Epub 2019 Nov 14.

Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia 27100, Italy.

The human genetic diversity of the Americas has been affected by several events of gene flow that have continued since the colonial era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored. Here, we compiled a genome-wide dataset of ∼12,000 individuals from twelve American countries and ∼6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected (1) the genetic structure, (2) the admixture profile, (3) the demographic history, and (4) sex-biased gene-flow dynamics of the Americas. We revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East, and to specific regions of Africa.
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http://dx.doi.org/10.1016/j.cub.2019.09.076DOI Listing
December 2019

Genetic variation study on fifteen STR loci in isolated Slovenian "Inland Island" human populations of the Selška Valley Region.

Homo 2019 Oct;70(2):129-137

International Burch University, Department of Genetics and Bioengineering, Sarajevo, Bosnia and Herzegovina.

This study was conducted to confirm preliminary anthropological research indicating the specificity of isolated Selška Valley populations and implement clear mapping of genetic distances between neighboring populations and similar "inland island" populations from the region. The sample consisted of 86 unrelated individuals born in the Selška Valley from the lowland villages (Bukovica, Ševlje, Dolenja Vas, Selca, Železniki and Zali Log) and the mountain villages (Podlonk, Prtovč, Spodnje Danje, Zgornja Sorica and Spodnja Sorica). The for mentioned 15 STR loci (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA) were analyzed and statistical analysis was applied to determine population-genetics and forensic parameters. The frequencies of 15 STR loci from isolated populations of Slovenian villages, Slovenia, Bosnian mountain villages and Bosnia and Herzegovina were analyzed to calculate genetic distances between them. Our results confirmed a similar genetic pattern between the Selška Valley mountain villages and Slovenian general population as well as Bosnian mountain villages and general Bosnian population. Even if the sample size was relatively small and examined populations were geographically isolated, observed genetic variation within the whole population was relatively high and comparable with neighboring populations. Additional analysis proved that the Selška Valley population is genetically closest to the Slovenian and Austrian populations. On the other hand, comparison with similarly patterned populations confirmed that this population could be recognized as "inland island" population in genetic terms.
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http://dx.doi.org/10.1127/homo/2019/1036DOI Listing
October 2019

A Candidate Gene Association Study of FKBP5 and CRHR1 Polymorphisms in Relation to War-Related Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):269-275

Department of Psychiatry, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia,

Background: Posttraumatic stress disorder (PTSD) is a highly frequent and disabling psychiatric condition among war-affected populations. The FK506-binding protein 5 (FKBP5) gene and the corticotropin-releasing hormone receptor 1 (CRHR1) gene have previously been implicated in an elevated risk of peritraumatic dissociation and PTSD development. Our aim was to investigate the association between FKBP5 and CRHR1 genotypes and PTSD diagnosis and severity among individuals who were affected by the Balkan wars during the 1990s.

Subjects And Methods: This study included participants with current PTSD, remitted PTSD and healthy volunteers (N=719, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). FKBP5 rs1360780 and CRHR1 rs17689918 genotypes were determined using a KASP genotyping assay.

Results: Tests for deviation from Hardy Weinberg equilibrium showed no significant results. Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients. There were nominally significant associations under a dominant model between the rs1360780 C allele and PTSD diagnosis as well as symptom severity, which however, were not significant anymore after Bonferroni adjustment (α=0.002). For CRHR1 rs17689918 no significant associations were detected.

Conclusion: We found nominally, but not Bonferroni corrected significant associations between the FKBP5 polymorphism rs1360780 and PTSD susceptibility among individuals affected by the Balkan wars. For elucidating this gene's real resilience/vulnerability potential, environmental influences should be taken into account.
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http://dx.doi.org/10.24869/psyd.2019.269DOI Listing
June 2019

The Role of TaqI DRD2 (rs1800497) and DRD4 VNTR Polymorphisms in Posttraumatic Stress Disorder (PTSD).

Psychiatr Danub 2019 Jun;31(2):263-268

Department of Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo,

Background: Posttraumatic stress disorder (PTSD) is a complex stress related disorder, that follows a severe traumatic experience, characterized with an intense sense of terror, fear, and helplessness. The aim of this study is to identify associations of genetic variations within candidate genes DRD2 and DRD4 with various PTSD related phenotypes. PTSD lifetime and PTSD current subjects were analyzed separately, each of them were analyzed in a Case/Control design, as well as regarding BSI and CAPS within cases only.

Subjects And Methods: 719 (487 male, 232 female) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Hercegovina, Kosovo and Croatia were included in the study. Sociodemographic questionnaire, Clinician Administered PTSD Scale (CAPS) and the Brief Symptom Inventory (BSI) were used to collect clinical data.

Results: The DRD2 rs1800497 variant and a variable number tandem repeat (VNTR) located in exon three of DRD4 were investigated for association with PTSD. In case control analyses we did not identify any significant associations. Within the PTSD current patients, we identified an association of DRD2 rs1800497 with BSI in the genotypic and the recessive model with the T allele as the risk allele.

Conclusion: Our findings suggest that rs1800497 of DRD2 gene is involved in pathogenesis of PTSD.
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http://dx.doi.org/10.24869/psyd.2019.263DOI Listing
June 2019

Role of the Allelic Variation in the 5-Hydroxytryptamine Receptor 1A (HTR1A) and the Tryptophan Hydroxylase 2 (TPH2) Genes in the Development of PTSD.

Psychiatr Danub 2019 Jun;31(2):256-262

Department of Psychiatry, University Clinical Centre of Kosovo, Str, Hile Mosi, nr 11, 10000 Prishtina, Kosovo,

Background: Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology.

Subjects And Methods: 719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology.

Results: A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology.

Conclusions: Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.
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http://dx.doi.org/10.24869/psyd.2019.256DOI Listing
June 2019

Association of Neuropeptide S Receptor 1 and Glutamate Decarboxylase 1 Gene Polymorphisms with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):249-255

Institute of Kosovo Forensic Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo.

Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by highly traumatic experiences. The aim of this study was to investigate the influence of single nucleotide polymorphisms (SNPs) in the neuropeptide S receptor 1 (NPSR1) and the glutamate decarboxylase 1(GAD1) gene on PTSD and its psychopathological aspects among individuals affected by the Balkan wars during the 90s.

Subjects And Methods: This study was conducted as part of the South Eastern Europe (SEE) study on molecular mechanisms of PTSD. It comprised 719 participants (539 males), including those with current PTSD, remitted PTSD and healthy volunteers. Psychometric evaluation was performed using the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) andthe Brief Symptom Inventory (BSI). We examined NPSR1 single nucleotide polymorphism (SNP) rs324981 and GAD1 variant rs3749034 genotypes. Case-control analyses were carried out using logistical regression to determine genotype differences between all patients that had either current or remitted PTSD and control individuals. To analyse the influence of the analysed SNPs on PTSD severity, we performed linear regression analyses with CAPS and BSI within each of the two patient groups separately. All of the calculations were performed for additive allelic, recessive, dominant and genotypic models.

Results: We observed a nominally significant association for the major allele (G) of GAD1 rs3749034 with an increased risk to develop PTSD in a case control analysis in the recessive model (P=0.0315, odds ratio=0.47, SE=0.35). In contrast, a nominally significant association of the minor allele (A) with higher CAPS scores was identified within the patient group with lifetime PTSD in the dominant model (P=0.0372, β=6.29, SE=2.99). None of these results did withstand correction for multiple tests. No nominal significant results of GAD1 rs3749034 were found with regard to the intensity of psychological BSI symptoms. Case-control analyses of NPSR1 rs324981 revealed a nominally significant higher risk for homozygous T allele carriers to develop PTSD (P=0.0452) in the recessive model. On the other hand, the T allele showed a nominally significant association with higher BSI scores in patients suffering from lifetime PTSD in the recessive model (P=0.0434). Again, these results were not significant anymore after correction for multiple tests. No associations of NPSR1 rs324981 and CAPS score was identified.

Conclusion: The findings of this study provide some evidence that the NPSR1 and GAD1 polymorphisms might play a role in the development of war-related PTSD and its related psychological expressions. Further research is needed to elucidate the interactions of specific gene variants and environmental factors in the development of PTSD.
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http://dx.doi.org/10.24869/psyd.2019.249DOI Listing
June 2019

The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):241-248

Department of Clinical Biochemistry, University Clinical Centre of Kosovo, Prishtina, Kosovo.

Background: Posttraumatic stress disorder (PTSD) is a disorder that occurs in some people who have experienced a severe traumatic event. Several genetic studies suggest that gene encoding proteins of catechol-O-methyl-transferase (COMT) may be relevant for the pathogenesis of PTSD. Some researchers suggested that the elevation of interleukin-6 (IL6) correlates with major depression and PTSD. The aim of this study was to investigate whether the single nucleotide polymorphisms COMT rs4680 (Val158Met) and IL6 rs1800795 are associated with PTSD and contribute to the severity of PTSD symptoms.

Subjects And Methods: This study comprised 747 participants that experienced war between 1991 and 1999 in the South Eastern Europe conflicts. COMT rs4680 (Val158Met) and IL6 rs1800795 genotypes were determined in 719 participants (369 with and 350 without PTSD). The Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) questionnaire and the Brief Symptom Inventory (BSI) were used for data collection.

Results: Regarding the COMT gene polymorphism, the results of the regression analyses for BSI total score were significant in the lifetime PTSD group in the dominant (P=0.031) and the additive allelic model (P=0.047). Regarding the IL6 gene, a significant difference was found for the recessive model predicting CAPS total score in the lifetime PTSD group (P=0.048), and indicated an association between the C allele and higher CAPS scores. n the allelic, genotypic and rezessive model, the results for BSI total score were significant in the lifetime PTSD group (P=0.033, P=0.028 and P=0.009), suggesting a correlation of the C allele with higher BSI scores.

Conclusion: Although our nominally significant results did not withstand correction for multiple tests they may support a relevance of the COMT (Val158Met) and IL6 rs1800795 polymorphism for aspects of PTSD in war traumatized individuals.
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http://dx.doi.org/10.24869/psyd.2019.241DOI Listing
June 2019

Associations between Polymorphisms in the Solute Carrier Family 6 Member 3 and the Myelin Basic Protein Gene and Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):235-240

Community Health Center Zivinice, Alije Izetbegovica 17, 75270 Zivinice, Bosnia & Herzegovina,

Background: Previous research showed inconsistent results concerning a possible association between solute carrier family 6 member 3 (SLC6A3) gene polymorphisms and dopamine symptoms of posttraumatic stress disorder (PTSD). Several studies also indicate that the myelin basic protein (MBP) gene is of importance in the etiology of several psychiatric disorders. The aim of this study was to investigate the relation of distinct SLC6A3 and MBP gene polymorphisms with PTSD and whether SLC6A3 and MBP genotypes contribute to PTSD symptom severity.

Subjects And Methods: The study included 719 individuals who had experienced war trauma in the South Eastern Europe (SEE). Genotypes of variable number tandem repeat (VNTR) polymorphism within the SLC6A3 gene were assessed in 696 participants, and the single nucleotide polymorphism (SNP) rs12458282 located within the MBP gene region was genotyped in a total of 703 subjects. The Mini International Neuropsychiatric Interview, the Clinical Administrated PTSD Scale (CAPS) and Brief Symptom Inventory (BSI), were used for data collection.

Results: No significant differences concerning the investigated SLC6A3 and MBP polymorphisms was identifiable between PTSD and non PTSD participants. Also we could not detect significant influence of these distinct SLC6A3 and MBP alleles on the severity of PTSD symptoms (CAPS) or BSI scores. However, the results of MBP rs12458282 within the patients with lifetime PTSD may point to a possible correlation of the major allele (T) with elevated CAPS scores.

Conclusions: Our results do not support an association of the analysed SLC6A3 and MBP gene polymorphisms with PTSD in war traumatized individuals. We found that there is a possibility for a correlation of the T allele rs12458282 within the MBP gene with higher CAPS scores in lifetime PTSD patients which would need to be tested in a sample providing more statistical power.
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http://dx.doi.org/10.24869/psyd.2019.235DOI Listing
June 2019

Associations of Gene Variations in Neuropeptide Y and Brain Derived Neurotrophic Factor Genes with Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):227-234

International Burch University, Department of Genetics and Bioengineering, Francuske revolucije bb, 71000 Sarajevo, Bosnia and Herzegovina,

Background: Individuals who are exposed to traumatic events are at an increased risk of developing posttraumatic stress disorder (PTSD), a condition during which an individual's ability to function is impaired by emotional responses to memories of those events. The gene coding for neuropeptide Y (NPY) and the gene coding for brain-derived neurotrophic factor (BDNF) are among the number of candidate gene variants that have been identified as potential contributors to PTSD. The aim of this study was to investigate the association between NPY and BDNF and PTSD in individuals who experienced war-related trauma in the South Eastern Europe (SEE) conflicts (1991-1999).

Subjects And Methods: This study included participants with current and remitted PTSD and healthy volunteers (N=719, 232 females, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administered PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). DNA was isolated from whole blood and genotyped for NPY rs5574 via PCR - RFLP and NPY rs16147 and BDNF rs6265 using the KASP assay.

Results: Tests for deviation from Hardy-Weinberg equilibrium showed no significant results. Analyses at the categorical level yielded no associations between the affected individuals and all three SNPs when compared to controls. Within lifetime PTSD patients, the major alleles of both NPY variants showed a nominally significant association with higher CAPS scores (p=0.007 and p=0.02, respectively). Also, the major allele of rs5574C>T was associated with higher BSI scores with a nominal significance among current PTSD patients (p=0.047). The results did not withstand a Bonferroni adjustment (α=0.002).

Conclusion: Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction.
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http://dx.doi.org/10.24869/psyd.2019.227DOI Listing
June 2019

Genetic Susceptibility to Posttraumatic Stress Disorder: Analyses of the Oxytocin Receptor, Retinoic Acid Receptor-Related Orphan Receptor A and Cannabinoid Receptor 1 Genes.

Psychiatr Danub 2019 Jun;31(2):219-226

Department of Psychiatry, Clinical Center University Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina,

Background: Exposure to life-threatening events is common and everyone will most likely experience this type of trauma during their lifetime. Reactions to these events are highly heterogeneous and seems to be influenced by genes as well. Some individuals will develop posttraumatic stress disorder (PTSD), while others will not. In this study, our aim was to analyze the correlation between single nucleotide polymorphisms (SNPs) within the oxytocin receptor (OXTR) gene (rs53576 and rs2254298), the RAR-related orphan receptor A (RORA) gene (rs8042149) and the cannabinoid receptor 1 (CNR1) gene (rs1049353) and PTSD. All candidate genes have been previously associated with stress related disorders and the reaction to traumatic events.

Subjects And Methods: Participants (N=719) have been exposed to war-related trauma during the war in South-Eastern Europe (Bosnia and Herzegovina, Croatia and Kosovo). We correlated the presence and absence of current and lifetime PTSD as well as PTSD severity (Clinician Administered PTSD scale (CAPS)) and current psychopathology (Brief Symptom Inventory (BSI) score) with the mentioned SNPs. DNA was isolated from whole blood and genotyped for OXTR rs2254298 and rs53576 following previously published protocols, for RORA rs8042149 via PCR-RFLP and CNR1 rs1049353 via KASP.

Results: Nominally significant results were found for OXTR rs53576 in connection with the CAPS and BSI scores within lifetime PTSD patients. The additive allelic model indicated that G allele carriers achieved lower CAPS (p=0.0090) and BSI (p=0.0408) scores than participants carrying one or two copies of the A allele. These results did not withstand correction for multiple tests. No significant results were observed for OXTR rs2254298, RORA rs8042149 and CNR1 rs1049353 although the results for RORA showed a slight tendency that rs8042149 may influence the level of BSI scores in current PTSD patients.

Conclusions: This study points to a role of the OXTR gene in PTSD and the related psychopathology following war related trauma.
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http://dx.doi.org/10.24869/psyd.2019.219DOI Listing
June 2019

Association Analysis of Maoa and Slc6a4 Gene Variation in South East European War Related Posttraumatic Stress Disorder.

Psychiatr Danub 2019 Jun;31(2):211-218

Department of Psychiatry, University Clinical Centre Tuzla, Rate Dugonjića bb, 75000 Tuzla, Bosnia and Herzegovina,

Background: The aim of this study is to investigate the association of gene variations of the monoamine oxidase A (MAOA) and the serotonin transporter solute carrier family 6 member 4 (SLC6A4) gene with posttraumatic stress disorder (PTSD) severity and coping strategies in patients with war related PTSD.

Subjects And Methods: The study included 747 individuals who had experienced war trauma in the South Eastern Europe conflicts between 1991 and 1999. Genotyping of the MAOA VNTR and SLC6A4 tandem repeat polymorphism in combination with rs25531 was done in 719 participants: 232 females and 487 males. Among them, 369 have had current or lifetime PTSD and 350 have had no PTSD symptoms. For psychometric approach we used the Clinician Administrated PTSD Scale (CAPS), the Brief Symptom Inventory (BSI), the adapted Hoffman-Lazarus Coping scale and a basic socio-demographic data questionnaire.

Results: There were no significant intergroup (PTSD versus non PTSD) differences in the genotype distribution of MAOA and SLC6A4 gene polymorphisms. The primary finding of our study was that the MAOA short allele (MAOA-S) was nominally significantly associated with the severity of PTSD symptoms in the total subgroup of participants with lifetime PTSD; males for symptoms of hyperarrousal and females with symptoms of re-experience and hyperarousal. In our research the male subsample with current PTSD and MAOA-S genotype had nominally significantly higher scores for some positive coping strategies compared to those carrying the long allele genotype (MAOA-L). There was no significant association between the severity of PTSD symptoms, BSI phenotype, coping scores and the SLC6A4 genotype.

Conclusion: The present results support the notion that MAOA VNTR gene variation modulates development and recovery of posttraumatic stress disorder in a war traumatised population, but did not support a connection between SLC6A4 gene variations and war related PTSD.
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http://dx.doi.org/10.24869/psyd.2019.211DOI Listing
June 2019

Population study of thrombophilic markers and pharmacogenetic markers of warfarin prevalence in Bosnia and Herzegovina.

Croat Med J 2019 Jun;60(3):212-220

Adna Ašić, Department of Genetics and Bioengineering, International Burch University, Francuske revolucije bb, 71210 Ilidža, Sarajevo, Bosnia and Herzegovina,

Aim: To investigate the prevalence of common genetic variants that can serve as markers of thrombophilia and warfarin pharmacogenetics in Bosnia and Herzegovina.

Methods: The study was performed between August and October 2017 on 130 healthy unrelated adult volunteers from Bosnian-Herzegovinian population sample. The prevalence of the following genetic variants was determined: F5 c.1601G>A (factor V Leiden), F2 c.*97G>A (factor II or prothrombin mutation), F13A1 (factor XIII) c.103G>T, MTHFR (methylenetetrahydrofolate reductase) c.665C>T and c.1286A>C, as well as PAI-1 (plasminogen activator inhibitor 1) c.-816A>G and c.-844G>A as markers of thrombophilia risk, and *2 and *3 alleles of CYP2C9 (cytochrome P450 2C9) and five variants of VKORC1 (vitamin K epoxide reductase complex subunit 1) as markers of warfarin pharmacogenetics. DNA was isolated from buccal swabs using salting out method, while genotyping was performed using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.

Results: Minor allele frequencies for two main thrombophilia risk factors, F5 c.1601G>A and F2 c.*97G>A were 0.023 and 0.008, respectively. Combined data for the markers of warfarin pharmacogenetics imply that 57.4% study participants can be expected to metabolize warfarin at an extensive, 40.3% at intermediate, and 2.3% at a poor rate.

Conclusion: This study reports the first extensive population genetic data for thrombophilia and warfarin pharmacogenetic markers in Bosnia and Herzegovina. Allele frequencies of genetic variants are within the general average for European populations, and their presence implies the necessity of introduction of personalized medicine in warfarin-mediated antithrombotic therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563168PMC
June 2019

Y chromosome genetic data defined by 23 short tandem repeats in a Serbian population on the Balkan Peninsula.

Ann Hum Biol 2019 Feb 24;46(1):77-83. Epub 2019 Apr 24.

e Department of Genetics and Bioengineering , International Burch University, Francuske revolucije bb , Ilidža , Bosnia and Herzegovina.

Background: Serbs mainly live in the territory of the recently re-established state of Serbia. However, the turbulent history in the Balkan Peninsula has led to settlement of Serbs not only within present day Serbia, but also in different parts of neighbouring countries.

Aim: To define polymorphisms of 23 Y-chromosomal short tandem repeat (STR) loci in a modern Serbian population from the central part of the Balkan Peninsula.

Subjects And Methods: The reference sample consisted of 303 men declared as Serbs over three generations. Localities of the collected materials include the territories of Serbia, Bosnia and Herzegovina, Croatia and Montenegro. DNA samples were typed using the PowerPlexY23 amplification kit.

Results: The highest locus diversity was observed for DYS385 and DYS481. In this study the most abundant haplogroups were I2a, E1b1b, R1a and I1. The largest genetic distances between the Serbs and other close Southern Slavs were for the Macedonians and Slovenians.

Conclusion: This study is the first one to define STR polymorphism of Serbian people not only from Serbia but also from other parts of the Balkan Peninsula. The presented genetic data may be useful in further examinations of the genesis and genetic structuring of the present-day Serbian gene pool.
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http://dx.doi.org/10.1080/03014460.2019.1584242DOI Listing
February 2019

Association Between - 675 ID, 4G/5G PAI-1 Gene Polymorphism and Pregnancy Loss: A Systematic Review.

Acta Inform Med 2018 Oct;26(3):156-159

International Burch University, Bosnia and Herzegovina.

Introduction: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss.

Aim: Therefore, we decided to investigate the -675 ID, 4G/5G as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 -1 gen, 4G/5G gene polymorphism, gene locus 4G/5G polymorphism.

Results: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001).

Conclusions: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.
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http://dx.doi.org/10.5455/aim.2018.26.156-159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195400PMC
October 2018

Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives.

Per Med 2018 05 16;15(3):209-221. Epub 2018 May 16.

St. Catherine Specialty Hospital, Zagreb & Zabok, Croatia.

Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants.
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http://dx.doi.org/10.2217/pme-2017-0092DOI Listing
May 2018

Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)-PTSD Study.

Int J Neuropsychopharmacol 2018 05;21(5):423-432

Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.

Background: Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity.

Methods: Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters.

Results: In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D).

Conclusions: The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding personalized treatment decisions on the use of antiadrenergic agents.
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http://dx.doi.org/10.1093/ijnp/pyx111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932467PMC
May 2018

A glimpse at the intricate mosaic of ethnicities from Mesopotamia: Paternal lineages of the Northern Iraqi Arabs, Kurds, Syriacs, Turkmens and Yazidis.

PLoS One 2017 3;12(11):e0187408. Epub 2017 Nov 3.

Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina.

Widely considered as one of the cradles of human civilization, Mesopotamia is largely situated in the Republic of Iraq, which is also the birthplace of the Sumerian, Akkadian, Assyrian and Babylonian civilizations. These lands were subsequently ruled by the Persians, Greeks, Romans, Arabs, Mongolians, Ottomans and finally British prior to the independence. As a direct consequence of this rich history, the contemporary Iraqi population comprises a true mosaic of different ethnicities, which includes Arabs, Kurds, Turkmens, Assyrians, and Yazidis among others. As such, the genetics of the contemporary Iraqi populations are of anthropological and forensic interest. In an effort to contribute to a better understanding of the genetic basis of this ethnic diversity, a total of 500 samples were collected from Northern Iraqi volunteers belonging to five major ethnic groups, namely: Arabs (n = 102), Kurds (n = 104), Turkmens (n = 102), Yazidis (n = 106) and Syriacs (n = 86). 17-loci Y-STR analyses were carried out using the AmpFlSTR Yfiler system, and subsequently in silico haplogroup assignments were made to gain insights from a molecular anthropology perspective. Systematic comparisons of the paternal lineages of these five Northern Iraqi ethnic groups, not only among themselves but also in the context of the larger genetic landscape of the Near East and beyond, were then made through the use of two different genetic distance metric measures and the associated data visualization methods. Taken together, results from the current study suggested the presence of intricate Y-chromosomal lineage patterns among the five ethic groups analyzed, wherein both interconnectivity and independent microvariation were observed in parallel, albeit in a differential manner. Notably, the novel Y-STR data on Turkmens, Syriacs and Yazidis from Northern Iraq constitute the first of its kind in the literature. Data presented herein is expected to contribute to further population and forensic investigations in Northern Iraq in particular and the Near East in general.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187408PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669434PMC
November 2017

Y-Chromosome Haplogroups in the Bosnian-Herzegovinian Population Based on 23 Y-STR Loci.

Hum Biol 2016 Jul;88(3):201-209

1 Department of Genetics and Bioengineering, International Burch University, Sarajevo, Bosnia and Herzegovina.

In a study of the Bosnian-Herzegovinian (B&H) population, Y-chromosome marker frequencies for 100 individuals, generated using the PowerPlex Y23 kit, were used to perform Y-chromosome haplogroup assignment via Whit Athey's Haplogroup Predictor. This algorithm determines Y-chromosome haplogroups from Y-chromosome short tandem repeat (Y-STR) data using a Bayesian probability-based approach. The most frequent haplogroup appeared to be I2a, with a prevalence of 49%, followed by R1a and E1b1b, each accounting for 17% of all haplogroups within the population. Remaining haplogroups were J2a (5%), I1 (4%), R1b (4%), J2b (2%), G2a (1%), and N (1%). These results confirm previously published preliminary B&H population data published over 10 years ago, especially the prediction about the B&H population being a part of the Western Balkan area, which served as the Last Glacial Maximum refuge for the Paleolithic human European population. Furthermore, the results corroborate the hypothesis that this area was a significant stopping point on the "Middle East-Europe highway" during the Neolithic farmer migrations. Finally, since these results are almost completely in accordance with previously published data on B&H and neighboring populations generated by Y-chromosome single nucleotide polymorphism analysis, it can be concluded that in silico analysis of Y-STRs is a reliable method for approximation of the Y-chromosome haplogroup diversity of an examined population.
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http://dx.doi.org/10.13110/humanbiology.88.3.0201DOI Listing
July 2016

Allele frequencies of 15 STR loci in Bosnian and Herzegovinian population.

Croat Med J 2017 Jun;58(3):250-256

Amela Pilav, Laboratory for Forensic Genetics, University of Sarajevo Institute for Genetic Engineering and Biotechnology, Zmaja od Bosne 8, (Kampus), 71000 Sarajevo, Bosnia and Herzegovina,

Aim: To determine newest the most accurate allele frequencies for 15 short tandem repeat (STR) loci in the Bosnian and Herzegovinian population, calculate statistical parameters, and compare them with the relevant data for seven neighboring populations.

Methods: Genomic DNA was obtained from buccal swabs of 1000 unrelated individuals from all regions of Bosnia and Herzegovina. Genotyping was performed using PowerPlex® 16 System to obtain allele frequencies for 15 polymorphic STR loci including D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX, and FGA. The calculated allele frequencies were also compared with the data from neighboring populations.

Results: The highest detected value of polymorphism information content (PIC) was detected at the PentaE locus, whereas the lowest value was detected at the TPOX locus. The power of discrimination (PD) values had similar distribution, with Penta E showing the highest PD of 0.9788. While D18S51 had the highest value of power of exclusion (PE), the lowest PE value was detected at the TPOX locus.

Conclusion: Upon comparison of Bosnian and Herzegovinian population data with those of seven neighboring populations, the highest allele frequency differentiation was noticed between Bosnian and Herzegovinian and Turkish population at 5 loci, the most informative of which was Penta E. The neighbor-joining dendrogram constructed on the basis of genetic distance showed grouping of Slovenian, Austrian, Hungarian, and Croatian populations. Bosnian and Herzegovinian population was between the mentioned cluster and Serbian population. To determine more accurate distribution of allelic frequencies and forensic parameters, our study included 1000 unrelated individuals from all regions of Bosnia and Herzegovina, and our findings demonstrated the applicability of these markers in both forensics and future population genetic studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470122PMC
http://dx.doi.org/10.3325/cmj.2017.58.250DOI Listing
June 2017

DNA Identification of Commingled Human Remains from the Cemetery Relocated by Flooding in Central Bosnia and Herzegovina.

J Forensic Sci 2018 Jan 11;63(1):295-298. Epub 2017 May 11.

Francuske revolucije bb, International Burch University, Francuske revolucije bb, Sarajevo, Bosnia and Herzegovina.

The floods in Bosnia and Herzegovina in May 2014 caused landslides all over the country. In the small village of Šerići, near the town of Zenica, a landslide destroyed the local cemetery, relocated graves, and commingled skeletal remains. As the use of other physical methods of identification (facial recognition, fingerprint analysis, dental analysis, etc.) was not possible, DNA analysis was applied. DNA was isolated from 20 skeletal remains (bone and tooth samples) and six reference samples (blood from living relatives) and amplified using PowerPlex Fusion and PowerPlex Y23 kits. DNA profiles were generated for all reference samples and 17 skeletal remains. A statistical analysis (calculation of paternity, maternity, and sibling indexes and matching probabilities) resulted in 10 positive identifications. In this study, 5 individuals were identified based on one reference sample. This has once again demonstrated the significance of DNA analysis in resolving the most complicated cases, such as the identification of commingled human skeletal remains.
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http://dx.doi.org/10.1111/1556-4029.13535DOI Listing
January 2018

Prevalence of F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms in Bosnian women with pregnancy loss.

Bosn J Basic Med Sci 2017 Nov 20;17(4):309-314. Epub 2017 Nov 20.

Institution of Health Protection of Women and Motherhood Canton Sarajevo, Sarajevo, Bosnia and Herzegovina.

The relationship between genetic risk factors of thrombophilia and pregnancy loss (PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Although, the frequencies of these polymorphisms were reported in different populations, such studies have not yet been performed in Bosnian population. In this study, we determined the prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133) polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (±5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age 31.4 (±6.7) years] with at least one live-born child were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was significantly higher in women with venous thrombosis (VT) compared to women without VT (p = 0.047 and p = 0.001, respectively). There was no significant difference in the distribution of MTHFR genotypes and alleles between these two groups. In addition, we observed no significant differences in the genotype and allele frequencies between the group with PL and control group, for all investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2), and 677T (MTHFR) reported in this study are consistent with the data obtained for other European countries, however, we were not able to confirm the association between the three polymorphisms and PL in Bosnian women.
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http://dx.doi.org/10.17305/bjbms.2017.1954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708901PMC
November 2017

Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

Environ Res 2017 07 12;156:665-673. Epub 2017 May 12.

Department of Genetics and Bioengineering, International Burch University, Francuske revolucije bb, Ilidza, 71210 Sarajevo, Bosnia and Herzegovina; Institute for Anthropologic Research, Ljudevita Gaja 32, 10000 Zagreb, Croatia.

The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties.
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http://dx.doi.org/10.1016/j.envres.2017.04.032DOI Listing
July 2017

Detection of cytosine and CpG density in proto-oncogenes and tumor suppressor genes in promoter sequences of acute myeloid leukemia.

Nucleosides Nucleotides Nucleic Acids 2017 Apr 21;36(4):302-316. Epub 2017 Mar 21.

a Department of Genetics and Bioengineering , International Burch University , Sarajevo , Bosnia and Herzegovina.

Aberrant methylation is one of the driving forces of cancer genome development. Although the rate of methylation appears massively variable across the genome, it is mainly observed in histone modification, chromatin organization, DNA accessibility, or promoter sequence. Methylation of promoter sequence occurs mostly to cytosine nucleotides, which can affect transcription factors' binding affinities. In this study, we demonstrated that cytosine repeats (C types density), consisting of CC, CCC, CCCC, CCCCC, CCCCCC, CCCCCCC motifs and CpG islands density in 25 proto-oncogenes, tumor suppressor genes and control genes may play a role in the pathogenesis of acute myeloid leukemia. The promoter sequences were divided into a 100 nucleotide window from -500 to +100 nucleotides and 20 nucleotide window from -100 to +100. Each window is analyzed to find the higher C type and CpG islands density, which may cause the increased methylation in the promoter sequence. Our novel findings show that promoter sequence cytosine repeats and CpG density increase closer to transcription sites, especially just before and after the transcription start site (TSS). The results demonstrate that cytosine density increases while proto-oncogenes and TSG promoter sequences are closer to TSS 50.8% and 41.0% respectively, if (-500 to -200) and (-100 to +100) windows of the nucleotide sequences are compared. This proves that around TSS location has special nucleotide motifs and could be an important implication for our understanding of potential methylating locations in promoters.
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http://dx.doi.org/10.1080/15257770.2017.1279738DOI Listing
April 2017

Molecular diversity of 23 Y-chromosome short tandem repeat loci in the population of Tuzla Canton, Bosnia and Herzegovina.

Ann Hum Biol 2017 Aug 30;44(5):419-426. Epub 2016 Nov 30.

a Department of Biology, Faculty of Natural Sciences and Mathematics , University of Tuzla , Tuzla , Bosnia and Herzegovina.

Background: Tuzla Canton is the most populated region in the ethnically mixed territory of Bosnia and Herzegovina, whose genetic analysis could provide an insight into past demographic events.

Aim: Analysis of 23 Y-chromosome STR markers in the population of Tuzla Canton and investigation of the genetic relationship of the male population of the Tuzla Canton and that of the larger Bosnian and Herzegovinian population as well as neighbouring and other European populations.

Subjects And Methods: The study was conducted among 100 unrelated healthy adult males from Tuzla Canton that have been genotyped using 23 Y-STR loci included in the PowerPlex Y23 kit. Statistical parameters such as haplotype diversity and allele frequencies were calculated, as well as the R-based genetic distances between the new dataset and those from Bosnia and Herzegovina and elsewhere, which were then visualised through multi-dimensional scaling plot and neighbour-joining phylogenetic tree analyses.

Results: The PowerPlex Y23 kit has shown high discrimination capacity, as all 100 individuals have unique haplotypes. The newly incorporated loci seem to be highly informative. Population comparison reveals no statistically significant differences between the study population and the general Bosnian-Herzegovinian population, and between the study population and neighbouring populations.

Conclusion: These results could be used as an additional investigation of the genetic relationship between the regional populations in Bosnia and Herzegovina and neighbouring human populations, as well as for further human population and forensic genetics studies.
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http://dx.doi.org/10.1080/03014460.2016.1259430DOI Listing
August 2017
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