Publications by authors named "Juraj Javor"

16 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
December 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

The association of rs703842 variants in CYP27B1 with multiple sclerosis susceptibility is influenced by the HLA-DRB1*15:01 allele in Slovaks.

J Neuroimmunol 2019 05 8;330:123-129. Epub 2019 Mar 8.

Department of Medical Biochemistry and BioMed, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic. Electronic address:

In this study, we analysed the association of rs703842 in CYP27B1 gene with multiple sclerosis (MS) risk and disability progression in a group of 496 MS patients and 521 controls. For the first time in Central European Slovak population, we found the rs703842 allele C to be protective factor against MS development (p = 1.09 × 10). Moreover, the risky genotypes TT and TC were showed to be associated with an increased MS risk, and this was aggravated by the homozygous carriage of the HLA-DRB1*15:01 allele (OR = 2.82 vs. 4.86, p < .0001). No association of rs703842 with MS disability progression or calcidiol serum level was found.
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http://dx.doi.org/10.1016/j.jneuroim.2019.03.006DOI Listing
May 2019

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

The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population.

Neurol Res 2018 Jul 5;40(7):607-614. Epub 2018 Apr 5.

c Jessenius Faculty of Medicine, Clinic of Neurology , Comenius University in Bratislava and University Hospital Martin , Martin , Slovak Republic.

Objective: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population.

Methods: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5, 7, 10, and 15 year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers.

Results: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5 year of disease duration was found in carriers of DRB1*07 allele (p  = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p  = 0.0305).

Discussion: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.
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http://dx.doi.org/10.1080/01616412.2018.1456711DOI Listing
July 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

ApaI, BsmI and TaqI VDR gene polymorphisms in association with multiple sclerosis in Slovaks.

Neurol Res 2016 Aug 23;38(8):678-84. Epub 2016 Jun 23.

b Department of Medical Biochemistry and BioMed, Jessenius Faculty of Medicine in Martin , Comenius University in Bratislava , Martin , Slovak Republic.

Objective: Vitamin D acts through vitamin D receptor (VDR) and has promising beneficial effects in the development and progression of multiple sclerosis (MS). The purpose of our study was to investigate the possible association of the VDR gene polymorphisms ApaI, BsmI and TaqI with the MS susceptibility and with the rate of disease disability progression in the Central European Slovak population.

Methods: The allele and genotype variants of ApaI, TaqI and BsmI VDR gene polymorphisms were analysed in 270 clinically diagnosed MS patients and 303 healthy controls. Genotyping was performed by polymerase chain reaction and restriction analysis. Patients were stratified by the rate of disease disability progression using MSSS scores.

Results: By logistic regression analysis, we revealed that genotype BB (AA) of BsmI VDR gene polymorphism is decreasing the risk of MS (BB (AA) vs Bb (AG) + bb (GG); OR = 0.59, 95% CI = 0.39-0.90, plog = 0.014). We did not identify any association of ApaI and TaqI polymorphisms neither with MS development nor with the disease progression.

Discussion: We showed for the first time that BsmI genotype BB (AA) is associated with the decreased susceptibility to MS in Slovak population. We propose the BsmI gene polymorphism to be one of the important genetic markers in evaluation of the risk of MS. However, our data suggest that VDR gene polymorphisms ApaI, BsmI and TaqI are not useful in the prediction of disease disability progression rate in MS in Slovaks.
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http://dx.doi.org/10.1080/01616412.2016.1200287DOI Listing
August 2016

The association of HLA-DRB1 and HLA-DQB1 alleles with genetic susceptibility to multiple sclerosis in the Slovak population.

Neurol Res 2015 8;37(12):1060-7. Epub 2016 Jan 8.

1 Clinic of Neurology, Jessenius Faculty of Medicine and University Hospital in Martin, Comenius University in Bratislava , Martin, Slovakia.

Objective: The aim of the present study was to assess the association between HLA-DRB1 and -DQB1 allele groups with the genetic predisposition to multiple sclerosis (MS) in the Caucasian Central European Slovak population.

Methods: A total of 282 unrelated patients with sporadic MS were enrolled in this case-control study. HLA-DRB1 and HLA-DQB1 allele groups were genotyped using a polymerase chain reaction with sequence-specific primers. The DRB1 and DQB1 allele carrier frequencies, genotypes and haplotype frequencies were compared between MS cases and healthy controls.

Results: Positive association with MS was found for alleles HLA-DRB1*15 (OR = 3.64; Pcor = 6.9x10-11), DRB1*03 (after elimination of carriers of DRB1*15, OR = 2.8; Pcor = 0.0029), DQB1*06 (OR = 1.99; Pcor = 7.0x10-4), genotypes HLA-DRB1*15/*15 (OR = 7.6; Pcor = 0.001) and DQB1*06/*06 (OR = 3.81; Pcor = 4.0x10-4) and for haplotype DRB1*15-DQB1*06 (OR = 3.03; Pcor = 0.001). Carriage of alleles DRB1*07 (OR = 0.53; Pcor = 0.04), DRB1*13 (OR = 0.39; Pcor = 4.0x10-4), DQB1*03 (OR = 0.46; Pcor = 1.0x10-4), genotypes HLA-DRB1*13/*11 (OR = 0.12; Pcor = 0.004), DQB1*05/*03 (OR = 0.39; Pcor = 0.035), DQB1*03/*03 (OR = 0.38; Pcor = 0.029) and haplotypes DRB1*13-DQB1*06 (OR = 0.47; Pcor = 0.0128) and DRB1*11-DQB1*03 (OR = 0.58; Pcor = 0.0352) was found to be protective against MS development.

Discussion: This is the first study performed to analyse the association of HLA-DRB1/DQB1 with susceptibility to MS in Slovakia. The results of our study confirm that HLA class II alleles, genotypes and haplotypes are associated with MS risk.
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http://dx.doi.org/10.1080/01616412.2015.1115212DOI Listing
October 2016

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

Gene 2015 Aug 9;568(1):50-4. Epub 2015 May 9.

Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Brazil; Centro de Terapia Celular e Molecular (NUCEL/NETCEM) da FMUSP, Brazil. Electronic address:

Background: A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association.

Methods: 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects.

Results: Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D.

Conclusion: Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D.
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http://dx.doi.org/10.1016/j.gene.2015.05.017DOI Listing
August 2015

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

Association of interleukin-10 gene promoter polymorphisms with susceptibility to acute pyelonephritis in children.

Folia Microbiol (Praha) 2014 Jul 22;59(4):307-13. Epub 2014 Jan 22.

Department of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborárske nám. 14, 81108, Bratislava, Slovakia,

Interleukin-10 (IL-10) is a potent inhibitor of leukocyte chemotaxis, bacterial killing in phagocytes and synthesis of pro-inflammatory cytokines and chemokines, and recent studies have suggested an important role for this immunoregulatory cytokine in the pathogenesis of urinary tract infections (UTIs). Therefore, the gene encoding IL-10 (IL10) is an attractive candidate for association studies attempting to identify susceptibility genes conferring risk of UTIs. In this case-control study, we aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the promoter region of IL10 with acute pyelonephritis in the Slovak population. Polymerase chain reaction with sequence-specific primers was used to analyse IL10 -1082A/G (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872) SNPs in 147 children with acute pyelonephritis and 215 healthy controls. Comparison of patients with healthy controls using the logistic regression analysis revealed significantly increased risk of developing recurrent attacks of acute pyelonephritis for -1082 G allele in a dominant genetic model GG (GG + AG vs. AA, P = 0.019, odds ratio (OR) = 2.26). A similar tendency was also found when the recurrent acute pyelonephritis subgroup was compared to episodic pyelonephritis cases (GG + AG vs. AA, P = 0.009, OR = 3.38). In conclusion, our results suggest that IL10 -1082 A/G SNP is a susceptibility factor for development of recurrent attacks of acute pyelonephritis.
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http://dx.doi.org/10.1007/s12223-014-0303-9DOI Listing
July 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

Inflammatory marker sTREM-1 reflects the clinical stage and respiratory tract obstruction in allergic asthma bronchiale patients and correlates with number of neutrophils.

Mediators Inflamm 2012 5;2012:628754. Epub 2012 Jul 5.

Institute of Immunology, Comenius University, Bratislava, Slovakia.

The knowledge that asthma is an inflammatory disorder has prompted us to investigate the plasma levels of a new inflammatory marker sTREM-1 that is released from the surfaces of activated neutrophils and monocytes. The plasma levels of sTREM-1 were analysed by a sandwich ELISA test in the cohort of 76 patients with allergic asthma bronchiale and 39 healthy controls. Our results revealed more than 3.5 times higher levels of sTREM-1 in AB patients (92.3 pg/mL ± 125.6) compared with healthy subjects (25.7 pg/mL ± 9.2; P = 0.0001). Higher levels of sTREM-1 were found also in patients with exacerbated AB (170.5 pg/mL ± 78.2) compared with nonexacerbated AB patients (59.1 ± 78.2; P < 0.0001), patients with respiratory tract obstruction (176.4 pg/mL ± 177.8), than those without obstruction (51.99 pg/mL ± 64.0; P < 0.0001) and patients with anti-IgE therapy (P < 0.0001). Levels of sTREM-1 correlated with number of leucocytes (P = 0.002), and absolute number of neutrophils (P = 0.001). Elevated plasma levels of sTREM-1 reflect the severity, state of exacerbation, presence of respiratory tract obstruction in AB patients and together with increased number of neutrophils point to the role of neutrophils in inflammation accompanying AB.
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http://dx.doi.org/10.1155/2012/628754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399449PMC
November 2012

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

Polymorphisms in the genes encoding TGF-beta1, TNF-alpha, and IL-6 show association with type 1 diabetes mellitus in the Slovak population.

Arch Immunol Ther Exp (Warsz) 2010 Oct 5;58(5):385-93. Epub 2010 Aug 5.

Department of Immunology, Faculty of Medicine, Comenius University, Odborarske nam. 14, 813 72 Bratislava 1, Slovakia.

Numerous cytokines have been shown to participate in the pathogenesis of type 1 diabetes (T1D). As gene polymorphisms can influence cytokine production or function, they may potentially contribute to genetic predisposition to the disease. The aim of this study was therefore to investigate the role of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine and cytokine receptor genes in genetic susceptibility to T1D. Polymerase chain reaction with sequence-specific primers was used to genotype cytokine SNPs and HLA-DRB1 alleles in 151 diabetics and 140 healthy individuals of Slovak origin. Univariate analysis showed that transforming growth factor (TGF)-beta1 codon 10 TT homozygotes were significantly more susceptible to developing T1D than C allele carriers (P (c) = 0.0066, OR = 2.46). Furthermore, tumor necrosis factor (TNF)-alpha -308 A allele carriers were also significantly overrepresented among the diabetics (P (c) = 0.0031, OR = 2.62); however, the association of the -308 A allele with T1D might be due to its strong linkage disequilibrium with the susceptibility allele HLA-DRB1*0301. An association was also found with interleukin (IL)-6 -174 G/C and nt565 G/A SNPs; however, its significance was lost when statistical correction was applied. These data suggest that the TGF-beta1 codon 10 SNP is among numerous genetic variations with small individual effects on T1D development. Moreover, a possible role of TNF-alpha and IL-6 SNPs cannot be ruled out, although their association with T1D was due to strong LD with the HLA class II susceptibility allele or did not withstand statistical correction, respectively.
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http://dx.doi.org/10.1007/s00005-010-0092-zDOI Listing
October 2010
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