Publications by authors named "Ivana Shawkatova"

10 Publications

  • Page 1 of 1

Impact of rs243865 and rs3025058 Polymorphisms on Clinical Findings in Alzheimer's Disease Patients.

Mediators Inflamm 2021 19;2021:5573642. Epub 2021 Apr 19.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of rs243865 and rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of rs243865 (-1306 C>T) and rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, = 0.036). The results of rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, = 0.045). In conclusion, our results suggest that rs243865 and rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.
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http://dx.doi.org/10.1155/2021/5573642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079184PMC
April 2021

Association of CD33 rs3865444:C˃A polymorphism with a reduced risk of late-onset Alzheimer's disease in Slovaks is limited to subjects carrying the APOE ε4 allele.

Int J Immunogenet 2020 Oct 24;47(5):397-405. Epub 2020 Apr 24.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late-onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid β42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25-0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61-1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C˃A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.
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http://dx.doi.org/10.1111/iji.12489DOI Listing
October 2020

TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population.

Int J Immunogenet 2018 Jul 16. Epub 2018 Jul 16.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

Tumour necrosis factor (TNF)-mediated signalling plays a key role in inflammatory and neurodegenerative processes leading to the development of multiple sclerosis (MS). Recent studies have highlighted the role of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) gene encoding the type 1 TNF receptor in the genetic predisposition to MS. This study aimed to validate the association of TNFRSF1A rs1800693 and rs4149584 polymorphisms with susceptibility to MS in the Slovak population and analyse their influence on age at disease onset, severity, and disability progression. Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype both TNFRSF1A polymorphisms in 541 MS patients and 724 healthy controls. Logistic regression analysis revealed a significantly increased risk of developing MS for the carriers of rs1800693 C allele (TC + CC vs. TT: pcorr = 0.005; OR = 1.61; 95% CI = 1.23-2.12), irrespective of sex and carriage of the major MS risk allele HLA-DRB1*15:01. On the other hand, no association could be found between rs4149584 and MS risk (GA + AA vs. GG: pcorr = 1.00; OR = 1.25; 95% CI = 0.71-2.21). Moreover, neither polymorphism was significantly associated with age at disease onset, MS Severity Score (MSSS) or MS Progression Index (PI) in any of the inheritance models. In conclusion, our results provide support for a sex- and HLA-DRB1*15:01-independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.
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http://dx.doi.org/10.1111/iji.12388DOI Listing
July 2018

A Novel Association of Polymorphism in the Gene Encoding the VLA-4 4 Subunit with Increased Risk of Alzheimer's Disease.

Mediators Inflamm 2018 27;2018:7623823. Epub 2018 Mar 27.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule 41, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the gene encoding the 4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped for gene SNP polymorphism rs113276800 (-269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for the -4, which is a known genetic factor associated with increased risk of AD developing. polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls ( ≤ 0.05). Following the -4 stratification of study groups, the association remained significant only in -4 noncarriers. Our study suggests a novel association of +3061A/G polymorphism with AD and its possible contribution to the disease pathology.
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http://dx.doi.org/10.1155/2018/7623823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892238PMC
October 2018

Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients.

Folia Microbiol (Praha) 2017 Jul 27;62(4):287-293. Epub 2017 Jan 27.

Institute of Immunology, Faculty of Medicine, Comenius University, Odborarske nam. 14, 813 72, Bratislava, Slovakia.

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.
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http://dx.doi.org/10.1007/s12223-017-0499-6DOI Listing
July 2017

The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01-negative individuals.

J Neurol Sci 2015 Feb 9;349(1-2):138-42. Epub 2015 Jan 9.

Department of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

C-C chemokine receptor 2 (CCR2) is one of the key players involved in the transmigration of mononuclear cells into the central nervous system (CNS) and subsequent development of multiple sclerosis (MS). The aim of the current study was to analyse the association of CCR2 +190 G/A (rs1799864) polymorphism with susceptibility to MS and its influence on the age at onset, severity and neurological disability in MS. CCR2 genotyping was carried out by a polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) in 301 MS patients and 342 healthy controls. Logistic regression analysis suggested a marginally significant association between MS and rs1799864 A allele (AA+GA vs. GG, P=0.047, OR=1.50, 95% CI=1.00-2.25), however, after stratification of study groups for the presence of HLA-DRB1*15:01 risk allele, this association could be found in HLA-DRB1*15:01-negative individuals only (AA+GA vs. GG, P=0.014, OR=1.84, 95% CI=1.13-2.98). Furthermore, there was no association between CCR2 polymorphism and clinical features of MS. In conclusion, our results suggest that CCR2 +190 G/A polymorphism may increase the susceptibility to MS, but its action seems to be restricted to individuals who do not possess the major risk allele HLA-DRB1*15:01.
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http://dx.doi.org/10.1016/j.jns.2015.01.002DOI Listing
February 2015

Donor non-specific MICA antibodies in renal transplant recipients.

Immunobiology 2014 Feb 23;219(2):109-12. Epub 2013 Aug 23.

Department of Immunology, Comenius University Faculty of Medicine, Odborárske nám. 14, 813 72 Bratislava, Slovakia.

Despite recent advances in solid organ transplantations, an antibody mediated rejection caused by donor specific antibodies is still a major problem in kidney graft survival. Besides HLA-induced humoral response, antibodies against MICA antigens have recently attracted attention because of their possible role in graft rejection. The aim of our study was to establish whether renal recipients produce antibodies against MICA molecules due to the transplantation and if they are specific for MICA antigens of the donors. MICA antibody screening was performed in 124 kidney recipient sera. 22 sera, that were found to be MICA antibody positive, were further examined for MICA antibody profiles and compared with donor MICA alleles. The analysis of MICA antibody positive sera showed mostly more complex reactivity patterns. A significant fraction of patient sera (59%) reacted not only with the donor MICA antigens, but also with other MICA patterns. A match between antibody specificities and MICA antigens was observed in 41% of renal recipients only. On the other hand, as much as in 36% of recipient sera were detected antibodies against their own MICA molecules. We did not prove a complete correlation between the recipient MICA antibody specificities and MICA antigens of the donor. We assume that MICA antibody induction occurs not only due to the allogeneic stimulation itself but also due to other factors that need to be elucidated.
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http://dx.doi.org/10.1016/j.imbio.2013.08.006DOI Listing
February 2014

HLA-C, DRB1 and DQB1 alleles involved in genetic predisposition to psoriasis vulgaris in the Slovak population.

Folia Microbiol (Praha) 2013 Jul 27;58(4):319-24. Epub 2012 Nov 27.

Department of Immunology, Comenius University School of Medicine, Nám. odborárov 14, Bratislava, Slovakia.

Psoriasis vulgaris is a complex chronic skin disease with immunological and genetic background. The most important predisposing genetic factors in psoriasis are genes of the human leukocyte antigen (HLA) region. Accumulative evidence has shown that several HLA alleles are closely associated with psoriasis; however, they tend to vary in different racial and ethnic backgrounds. One hundred forty-seven unrelated Slovak patients with psoriasis vulgaris (average age at onset 28 ± 14 years) were genotyped for the HLA-C, DQB1 and DRB1 alleles by the polymerase chain reaction using sequence-specific primers. Allele frequencies observed in the group of psoriatic patients were compared to those obtained in the ethnically matched control group comprising 194 subjects with no history of psoriasis. Susceptibility to psoriasis vulgaris in our study group is significantly associated with HLA-C*06 (odds ratio (OR) = 3.85), DRB1*07 (OR = 2.56) and DQB1*02 (OR = 1.09), respectively, whereas DRB*01 (OR = 0.05) is associated negatively. Hereby, we provide the first report on the association of HLA-C, DRB1 and DQB1 alleles with psoriasis in the Slovak population. Our findings confirm HLA-C*06 and DRB1*07 as the most important genetic risk factors for psoriasis. However, the role of HLA genes as causative in the pathogenesis of the disease remains unclear. Identification of genetic factors that increase the risk of psoriasis is a precondition that helps to elucidate the pathogenesis of this troubling disease and identify targets for a more specific and effective therapy.
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http://dx.doi.org/10.1007/s12223-012-0213-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683150PMC
July 2013

No association between cytokine gene polymorphism and risk of Alzheimer's disease in Slovaks.

Acta Neurobiol Exp (Wars) 2010 ;70(3):303-7

Institute of Immunology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

Clinical and immunopathological evidence support a potential role of inflammatory cytokines in Alzheimer's disease (AD). However, studies examining the association between cytokine gene polymorphisms and risk of developing AD yielded conflicting results. The objective of our study was to evaluate the association between the functional polymorphisms in the TNF-alpha, TGF-beta1, IL-10, IL-6 and IFN-gamma genes, respectively and the risk of AD in Slovak individuals. Fifty sporadic AD patients and 140 non-demented age-matched control subjects were genotyped in our case-control study. The observed allele and genotype frequencies in AD patients and controls did not reveal any statistically significant differences. In conclusion, our data suggest that there is no involvement of cytokine gene genetic variance in the development of AD in the Slovak population.
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January 2011

Gestational choriocarcinoma analyzed by polymerase chain reaction amplification of polymorphic VNTR and human leukocyte antigen regions.

Int J Gynaecol Obstet 2010 Aug 1;110(2):152-4. Epub 2010 May 1.

Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.

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http://dx.doi.org/10.1016/j.ijgo.2010.03.019DOI Listing
August 2010
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