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ABSTRACT: Prosthetic joint infection (PJI) is a serious complication of the total joint arthroplasty (TJA). Serum mannose-binding lectin (MBL), a pattern recognition receptor, is involved in antibacterial immune response. This study investigated whether functional variants of the MBL2 gene may be associated with the risk of PJI. MBL2 -550 (H/L, rs11003125), MBL2 -221 (Y/X, rs7096206) and MBL2 +54 (G/A, rs1800450) single nucleotide polymorphisms (SNP) were genotyped in 112 PJI patients and two control groups: 245 patients with aseptic TJA and 196 Czech population controls without TJA. Serum MBL concentration was assessed in PJI patients (n = 92) and aseptic TJA controls (n = 56). The distribution of MBL2 genotypes complied with the Hardy-Weinberg equilibrium in all investigated groups. Importantly, MBL2 -550 L allele (allelic frequency, 0.72) and LL genotype (genotype frequency, 0.51) were more frequent among PJI patients compared to aseptic TJA controls (L allele: 0.63, P = 0.016, P(c) = 0.048; LL genotype: 0.39, P = 0.037, P(c) > 0.05) and to Czech population controls (L allele: 0.61, P = 0.010, P(c) = 0.030; LL genotype: 0.35, P = 0.006, P(c) = 0.018), respectively. Regarding MBL protein, the MBL2 -550 L carriers presented with lower serum MBL concentrations than non-carriers (median; 593 vs 1876 ng/ml; P < 0.01). Similarly, the carriage of MBL2 -221 X and 54 A alleles was associated with lower serum MBL concentrations (P < 0.01). In conclusion, MBL2 -550 genetic variant(s) associated with low serum concentration of MBL protein can increase the risk of PJI.
Tissue Antigens 09/2012; 80(5):444-51. · 2.59 Impact Factor
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ABSTRACT: Schizophrenia is a severe psychiatric disease with inflammatory component. Several studies indicated the increased blood levels of proinflammatory interleukin-6 cytokine in schizophrenia. However, only limited studies explored the relationship between excess production and genetic variations of this cytokine in schizophrenia, and the results were controversial. Here, we investigated possible association of the interleukin-6 gene (IL6) rs1800795 (-174G/C) polymorphism with schizophrenia and relationship between this polymorphism and interleukin-6 protein (IL-6) blood levels. This polymorphism was found by other researchers to associate with different transcription rates and different plasma levels of IL-6. A total of 208 unrelated Armenians were genotyped by polymerase chain reaction with sequence-specific primers, and IL-6 levels were assessed by enzyme-linked immunosorbent assay. The IL6 rs1800795 alleles and genotypes in both groups were in Hardy-Weinberg (H-W) equilibrium. We found that rs1800795*C allele [38% vs 24%, P = 0.002, odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.18-2.14] and its carriers (62% vs 42%, P = 0.003, OR = 2.28, 95% CI: 1.13-1.94) were more frequent in patients than in controls. IL-6 in patients was 1.5-fold higher than in controls (mean ± SD: 6.41 ± 2.47 pg/ml vs 4.15 ± 1.42 pg/ml, P = 1.9E-19). In both groups, higher IL-6 in rs1800795 GG compared to rs1800795*C allele carriers was observed (GG vs GC + CC, patients: 7.02 ± 2.83 pg/ml vs 5.39 ± 1.2 pg/ml, P = 0.0006; controls: 5.21 ± 1.17 pg/ml vs 3.38 ± 1.03 pg/ml, P = 1.6E-15). In conclusion, we report an association of IL6 rs1800795 and higher IL-6 with schizophrenia. We also conclude that IL6 rs1800795*C allele is linked to increased IL-6 blood levels and may be a risk factor for schizophrenia development at least in Armenian population.
Tissue Antigens 05/2012; 80(2):136-42. · 2.59 Impact Factor
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ABSTRACT: In the recent genome-wide association study the polymorphisms of annexin A11 (ANXA11) gene were associated with susceptibility to sarcoidosis. Beside the replication of this finding and analysis of local ANXA11 expression in bronchoalveolar lavage cells, we wondered whether 'leading' ANXA11 rs1049550 (R230C) variant might also be related to the clinical manifestation of sarcoidosis. The study included 245 Czech patients with sarcoidosis and 254 healthy control subjects. The frequency of ANXA11(*)T allele was significantly lower in patients with sarcoidosis (35%) compared with controls (42%, P=0.04, odds ratio=0.77). Furthermore, ANXA11(*)T allele was less frequent in patients with the infiltration of lung parenchyma by comparison with those with isolated hilar lymphadenopathy (P=0.01). In line with the previous observation, ANXA11 mRNA expression was not deregulated in sarcoidosis and was independent from rs1049550 variant. In conclusion, ANXA11 rs1049550 single nucleotide polymorphism is the susceptibility marker in sarcoidosis, at least in Caucasians. Its role as a disease modifier should be independently replicated.
Genes and immunity 05/2011; 12(6):490-4. · 4.22 Impact Factor
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ABSTRACT: Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
European Respiratory Journal 05/2011; 38(5):1136-44. · 5.89 Impact Factor
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ABSTRACT: We determined the distribution of human leukocyte antigen-C (HLA-C) allelic groups in a cohort of psoriatic arthritis (PsA) patients and a control population of Romanian ethnicity. A nominal association of HLA-C*06 with susceptibility to PsA was observed [P = 0.014, p(corr) > 0.05, odds ratio (OR) 2.1, 95% confidence interval (CI) 1.08-4.46]. When subanalyzing data according to PsA clinical phenotypes, association was noticed between HLA-C*06 and PsA with psoriasis onset before 40 years (p(corr) = 0.013, OR 3.7, 95% CI 1.58-9). This first report from Romania confirmed the association of HLA-C*06 with type I psoriasis in PsA patients. Other study findings, such as the relationship between HLA-C*06 and spondylitis or the protective effect of HLA-C*07 for the polyarthritis clinical phenotype of PsA, are of preliminary character and require verification.
Tissue Antigens 04/2011; 77(4):325-8. · 2.59 Impact Factor
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Cytokine 01/2011; 53(1):13-4. · 3.02 Impact Factor
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ABSTRACT: C-reactive protein (CRP) is an inflammation marker implicated in the pathogenesis of schizophrenia. To investigate association of the CRP rs1417938, rs1800947, rs1205 variants with susceptibility to schizophrenia 208 unrelated Armenians (103 patients and 105 healthy controls) were genotyped. In this pilot study, none of studied variants was associated with schizophrenia.
International Journal of Immunogenetics 10/2010; 37(5):407-10. · 1.29 Impact Factor
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ABSTRACT: Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).
Bratislavske lekarske listy 01/2010; 111(8):420-5. · 0.40 Impact Factor
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ABSTRACT: Various polymorphisms of non-HLA genes have recently been investigated as candidate risk factors in allogeneic haematopoietic SCT (aHSCT). Our study aimed at exploring possible associations of IL6 and CCL2 single nucleotide polymorphisms (SNP) with aHSCT outcome. A total of 166 HLA-identical aHSCT pairs recruited in were genotyped for IL6 -174 G/C, IL6 -597 G/A, CCL2 -2518 A/G and CCL2 -2076 A/T SNPs by PCR with sequence-specific primers (PCR-SSP). The association between IL6 -174 GG genotype and increased risk of acute GVHD was found in whole study group (P=0.03) and in the subgroup of related aHSCT (P=0.01), association between IL6 -597 GG genotype and the occurrence of acute GVHD was detected only in the related aHSCT pairs (P=0.02). Furthermore, reduction in OS was revealed among recipients possessing IL6 -174(*)G allele in the group of related aHSCT pairs (P=0.04). Presence of CCL2 -2076 TT genotype was associated with decrease of OS (P=0.04) and increase of TRM (P=0.02) in patients transplanted by related donor. These results, in the context of previous findings, suggest that IL6 gene polymorphisms may be associated with aHSCT outcome, particularly in patients transplanted from a related donor.
Bone marrow transplantation 03/2009; 44(4):227-35. · 3.00 Impact Factor
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ABSTRACT: The objective of this study was to assess protein levels for candidate cytokines, chemokines, growth factors, matrix metalloproteinases and their inhibitors in bronchoalveolar lavage fluid (BALF) in patients with polar forms of pulmonary sarcoidosis, i.e. Löfgren's syndrome (LS) and more advanced chest X-ray (CXR) stage III disease. Twenty-four inflammatory molecules were analysed in unconcentrated BALF samples from 10 sarcoidosis patients with CXR stage III and 10 patients with LS by semiquantitative protein array. Four novel molecules [CC chemokine ligand (CCL)15, CCL16, macrophage migration inhibitory factor (MIF) and macrophage stimulating protein (MSP)], detected for the first time in association with sarcoidosis, were then quantified by enzyme-linked immunosorbent assay in a second cohort of 68 sarcoidosis patients and 17 control subjects. The protein levels of CCL15, CCL16, CCL24, CXCL8, CXCL9, CXCL10, interleukin-16, MIF, MSP and matrix metallopeptidase 1 were increased in CXR stage III patients when compared with patients with LS. CCL15 and MSP up-regulation in CXR stage III patients in comparison with LS patients and controls was confirmed by enzyme-linked immunosorbent assay. Moreover, MSP was associated with treatment requirement (P = 0.001) and CCL15 was elevated in patients with disease progression at 2-year follow-up (P = 0.016). CCL16 levels were increased in sarcoidosis versus controls (P < 0.05), but no difference was observed between patient subgroups. MIF up-regulation was not confirmed in a larger patient group. In conclusion, chemokines CCL15, CCL16 and MSP were found elevated for the first time in BALF from sarcoidosis patients; our results showed that CCL15 and MSP may affect disease course.
Clinical & Experimental Immunology 03/2009; 155(3):457-65. · 3.36 Impact Factor
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ABSTRACT: We investigated the MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) in Slovak cohort of patients with ischemic heart disease (IHD). Our study comprised 270 patients with IHD, out of them 92 with myocardial infarction (MI). We found that the frequencies of the mutant GG genotype in Slovak patients with IHD (10.7%; p=0.019) and MI (12.0%; p=0.046) were significantly higher than those in the control subjects (5.8%). After subdividing the groups according to the sex, statistically significant difference was found only in men (IHD: p=0.013, MI: p=0.009). We also found a higher rate of GG homozygous genotype in patients with early (< or =50 years of age) MI (18.4%; p=0.004)--statistically significant again only in men (23.1%; p=0.002). The frequencies of G alleles in IHD male patients (30.3%, p=0.046) and in early MI male patients (38.5%, p=0.019) were also statistically significantly higher than in control group. Our results confirm that IHD and MI are linked to MCP-1 -2518 (A/G) single nucleotide polymorphism (Tab. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.
Bratislavske lekarske listy 02/2009; 110(7):385-9. · 0.40 Impact Factor
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Z Kubistova, F Mrazek,
P A Lympany,
A L Lagan,
A Arakelyan,
E Kriegova,
K I Welsh,
V Kolek,
J Zatloukal,
B Hutyrova,
R M du Bois,
M Petrek
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF), a severe lung disease with unknown aetiology, is thought to have an important genetic component. Single nucleotide polymorphism, C5507G, of the complement receptor 1 (CR1) gene, which affects the number of CR1 molecules on erythrocytes, has been associated with susceptibility to IPF in a single European population. To replicate this finding, 53 Czech IPF patients with 203 Czech healthy control subjects and 70 English IPF patients with 149 English controls were investigated. In both populations, there were no significant differences in distribution of CR1 C5507G variants between IPF patients and their appropriate control groups. In conclusion, the association of the CR1 C5507G polymorphism with susceptibility to IPF was not reproducible in Czech and English populations.
Tissue Antigens 12/2008; 72(5):483-6. · 2.59 Impact Factor
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ABSTRACT: Several lines of evidence suggest that chemokines play an important role in asthma and allergy. We analysed polymorphisms at -2518A/G and -2076A/T of MCP-1 and V64I of CCR2 gene in healthy subjects (n = 306) and allergic patients (n = 332). Allele and genotype frequencies did not differ significantly between groups. Nevertheless, MCP-1 variants were associated with allergen sensitization. The results suggest that MCP-1, but not CCR2 gene variants, may participate in the pathogenesis of allergic phenotypes at least in the Caucasian population.
International Journal of Immunogenetics 12/2008; 36(1):69-72. · 1.29 Impact Factor
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ABSTRACT: Interleukin-6 (IL-6) is an important pro-inflammatory mediator implicated in immune-mediated complications of allogeneic haematopoietic stem cell transplantation (aHSCT). In accord with previous reports, this preliminary study on 56 donor-recipient pairs revealed IL-6-174 single nucleotide polymorphisms as a risk factor for the development of acute graft-versus-host disease and decreased survival after aHSCT.
International Journal of Immunogenetics 09/2008; 35(4-5):401-3. · 1.29 Impact Factor
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F Mrazek,
M Kvezereli,
E Garr,
Z Kubistova,
E Kriegova,
R Fillerova,
A Arakelyan,
H J T Ruven,
J Drabek,
J M M van den Bosch,
V Kolek,
K I Welsh,
J C Grutters,
R M du Bois,
M Petrek
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ABSTRACT: A single nucleotide polymorphism (SNP) C5507G of the complement receptor 1 (CR1) gene has been associated with genetic susceptibility to sarcoidosis in an Italian population. In order to provide further data on the possible involvement of CR1 gene polymorphisms in sarcoidosis, CR1 SNPs C5507G and A3650G were investigated in Czech (n = 210) and Dutch (n = 116) patients with sarcoidosis with ethnically matched groups of healthy control subjects (Czech, n = 203; Dutch, n = 112). CR1 C5507G and A3650G SNPs were not associated with susceptibility to sarcoidosis or its clinical course. Further, CR1 messenger RNA expression in bronchoalveolar lavage cells investigated by quantitative reverse transcriptase-polymerase chain reaction did not differ between sarcoidosis patients and control subjects and was not associated with the presence of the CR1 5507*G allele.
Tissue Antigens 02/2008; 71(1):77-80. · 2.59 Impact Factor
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International Journal of Immunogenetics 01/2008; · 1.29 Impact Factor
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E Kriegova,
A Tsyrulnyk,
A Arakelyan, F Mrazek,
M Ordeltova,
S Petzmann,
J Zatloukal,
V Kolek,
R M du Bois,
H Popper,
M Petrek
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ABSTRACT: CCX CKR is a decoy chemokine receptor that specifically binds the chemokines CCL19, CCL25 and CCL21. CCL19 was previously found to be upregulated in pulmonary sarcoidosis. We have, therefore, investigated CCX CKR expression in this inflammatory disease.
CCX CKR mRNA was semiquantitated using RT-PCR in unseparated bronchoalveolar (BAL) cells from sarcoidosis patients (S, n = 29) and healthy control subjects (C, n = 9). CCX CKR transcripts were upregulated in patients (mean +/- SEM); S, 0.82 +/- 0.10; C, 0.44 +/- 0.04; p = 0.01; this upregulation paralleled the disease course as assessed by the chest radiographic stage (p < 0.02). Immunocytochemistry localised the CCX CKR protein to ciliated bronchial cells. Flow cytometric fluorescent ligand uptake assay showed that these cells are able to internalize its ligand.
These observations implicate CCX CKR in the modulation of the inflammatory response in sarcoidosis.
Inflammation Research 10/2006; 55(10):441-5. · 2.11 Impact Factor
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ABSTRACT: Cytokine gene polymorphisms (CGP) have been implicated in the pathogenesis of immune-mediated diseases including transplant complications via their effect on cytokine production and regulation. This study aimed to determine population frequencies of selected cytokine single nucleotide polymorphisms in the healthy Czech population and compare them with the data from other selected European populations. CGP were genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the Heidelberg kit in 120 unrelated Czech healthy individuals. Chi-squared analysis was used to test for a deviation from Hardy-Weinberg equilibrium. Allelic and genotype frequencies and carriage rates were determined for 22 CGP located within 13 cytokine genes in total. The frequencies observed in this study were similar to those available from the other two geographically close Central European centres, but they differed for several CGP from the data reported in south European populations. The data on the distribution of 22 CGP in the healthy Czech population reported here may be utilized to investigate possible associations of CGP with diseases or transplantation outcome.
International Journal of Immunogenetics 09/2006; 33(4):261-7. · 1.29 Impact Factor
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ABSTRACT: A novel HLA-B (human leukocyte antigen-B) allele, HLA-B*4442, was identified both in a Czech patient with leukaemia and in his mother. The presence of a novel allele was initially suspected because conflicting results were obtained by serological and DNA typing techniques. The HLA typing using the polymerase chain reaction-sequence-specific primers (PCR-SSP) at the two-digit level indicated an allele belonging to the HLA-B*44 group, whereas serological typing indicated HLA-B21. Typing with PCR-sequence-specific oligonucleotides (PCR-SSO) resulted in a unique reaction pattern that could not be assigned to a known allele, PCR-SSP typing at the four-digit level did not match any known B*44 allele, either. The sequencing-based typing of the HLA-B locus then revealed the novel B*4442 allele that is identical with B*4405 except a single C-->G nucleotide exchange at position 572. This exchange results in an amino acid substitution from serine to tryptophan at position 167 of the expressed HLA-B protein. The B21 serological reactivity of the novel B*4442 allele product was confirmed by employing an additional serological panel of typing sera. Our findings support previous reports claiming that serine at the position 167 in the alpha-2 domain of the HLA-B protein is a major determinant of the HLA-B44(12) serological epitope.
International Journal of Immunogenetics 06/2006; 33(3):197-200. · 1.29 Impact Factor
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ABSTRACT: Monocyte chemoattractant protein (MCP)-1 is the key chemokine in the process of atheroslerotic vascular inflammation. Examining already reported association between coronary artery disease (CAD) and the SNP A/G in the MCP-1 gene (position -2518), 139 Czech patients with CAD manifested as myocardial infarction (MI) and 359 unrelated healthy control (C) subjects were genotyped by PCR-SSP. Genotype and allele frequencies were not different in MI and C groups (allele G: MI, 20.5%; C, 23.8%, OR = 0.8, P > 0.05). No differences were detected when the patients were subdivided based on sex or the age of MI first occurrence. Further, no relationship was observed between circulating MCP-1 levels and carriage of the G allele. The data do not support a role for the MCP-1 -2518 single nucleotide polymorphism in susceptibility to CAD manifested by myocardial infarction.
International Journal of Immunogenetics 11/2005; 32(5):315-8. · 1.29 Impact Factor
