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Katarzyna Bogunia-Kubik

Publications and source records attributed to Katarzyna Bogunia-Kubik.

14 recordsLinked to original sources
PubMed2025

The importance of dopamine levels and single-nucleotide polymorphism within COMT, DRD1 and DRD2 genes in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a prevalent sleep disorder that contributes to serious cardiovascular comorbidities. While the mechanical aspects of OSA are well-studied, its neurobiological underpinnings remain underexplored. In this study, we investigated the role of dopamine and its genetic modulators in OSA pathophysiology. PATIENTS AND METHODS: Serum dopamine levels were assessed in a cohort of 153 participants (96 OSA patients and 57 controls), and single-nucleotide polymorphisms (SNPs) in dopamine-related genes, including COMT, DRD1 and DRD2, were analysed in a cohort of 286 participants (141 OSA patients and 145 controls). RESULTS: Elevated serum dopamine levels were observed in OSA patients (p = 0.01), with dopamine levels correlating independently with OSA and male gender. Genotypic analysis identified the DRD2 rs1800497 T allele as a potential independent predictor of OSA severity (p = 0.011), hypopnea (p = 0.005) and arousals (p = 0.024). CONCLUSIONS: This study advances the understanding of OSA by identifying elevated dopamine levels and genetic variations in DRD2 rs1800497 as potential modulators of its occurrence and severity. These findings pave the way for personalized diagnostic and therapeutic approaches. By integrating neurobiology, genetics, and clinical practice, this research contributes to the evolving framework for precision medicine in sleep disorders.

Humans↗
PubMed2006

TGF-beta1 gene polymorphisms influence the course of the disease in non-Hodgkin's lymphoma patients.

Non-Hodgkin's lymphomas (NHL) constitute a heterogenous group of mainly B-cell lymphoproliferative diseases with different patterns of clinical behaviour. Biological mechanisms leading to development of NHL are not clearly understood. Transforming growth factor-beta1 (TGF-beta1) influences B cell growth and development. The present study aimed to determine whether there is an association between the polymorphic features located within the TGF-beta1 gene in NHL patients and progression of the disease. Two single nucleotide polymorphisms at positions 869 T/C (Leu10Pro) and 915 G/C (Arg25Pro) in the precursor region of the TGF-beta1 gene were determined in 55 NHL patients and 50 healthy individuals by PCR-SSP technique using commercial primers. In univariate analysis the presence of TGF-beta1 high producer genotypes (T/T G/G or T/C G/G) was found to significantly associate with an increased number of extranodal sites (11/30 vs 3/25, p=0.035 for two or more extranodal sites in patients having or lacking the TGF-beta1 high producer genotype, respectively). TGF-beta1 high producer genotype together with other clinical and biological factors (patient sex and age, stage and aggressiveness of the disease, presence of B symptoms, serum LDH level) were subjected to multivariate logistic regression analyses for the number of extranodal sites. Multivariate analysis confirmed the role of TGF-beta1 high producer genotype as a risk factor of NHL manifestation in two or more extranodal sites (OR=7.217, p=0.043) in addition to histological aggressiveness of the disease (OR=4.302, p=0.057). TGF-beta1 gene polymorphisms were found to associate with the course of the disease in NHL patients. TGF-beta1 high producer genotype appeared as an independent risk factor of extranodal manifestation of the disease.

Alleles↗
PubMed2006

The presence of IFNG 3/3 genotype in the recipient associates with increased risk for Epstein-Barr virus reactivation after allogeneic haematopoietic stem cell transplantation.

Recent studies have shown that interferon-gamma gene (IFNG) polymorphism constitutes a risk factor for acute and chronic graft-versus-host disease (GvHD) after allogeneic haematopoietic stem cell transplantation (HSCT). Patients with IFNG 3/3 have been found to be more prone to GvHD. This rather puzzling result, as 3/3 genotype is associated with a decreased IFN-gamma production, was investigated in the present study in the context of Epstein-Barr virus (EBV) reactivation. Microsatellite polymorphism (CA)n within the first intron of IFNG gene was assessed in 83 HSCT recipients and related to EBV load. Quantification of EBV copies was performed by a real-time polymerase chain reaction in peripheral blood cells taken from the patients 2-3 months after HSCT. It was found, that patients having IFNG 3/3 genotype presented with a high number of EBV copies (over 10/10(5) blood cells) when compared with the recipients with other IFNG genotypes (10/14 vs. 17/69, P < 0.001). This association was independent of recipient's age, underlying disease, conditioning regimen, type of donor, source of stem cells or pretransplant donor and recipient EBV serological status. Thus IFNG 3/3 genotype, known to be associated with a decreased IFN-gamma production, appeared as a factor significantly contributing to the risk of EBV reactivation after allogeneic HSCT.

Adolescent↗
PubMed2006

CCR5 deletion mutation and its association with the risk of developing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Recently published data have suggested a potential role of CC chemokine receptor-5 (CCR5) in a mouse model of graft-versus-host disease (GvHD). It has also been described that a 32-nucleotide deletion within the CCR5 gene (CCR5Delta32) leads to complete loss of functional CCR5 in subjects homozygous for this mutation and decreased expression in heterozygous individuals. We analyzed CCR5 genotypes and their relationship to transplant outcome. DESIGN AND METHODS: A total of 349 individuals, comprising 186 recipients and 163 donors of allogeneic hematopoietic stem cell transplants, were typed for CCR5 polymorphisms. RESULTS: Recipients carrying the CCR5Delta32 allele developed acute GvHD (grades I-IV) less frequently than did patients lacking the CCR5 deletion mutation (11/35 vs. 76/151, p=0.033). This association was still valid after correcting for other known variables (recipient age, donor-recipient gender relation, type of donor, conditioning regimen, diagnosis, stem cell source and GvHD prophylaxis) by logistic regression (OD=0.391, p=0.023). Transplantation from a donor other than a matched sibling (OD=2.007, p=0.028), recipient age (OD=2.117, p=0.041) and myeloablative conditioning regimen (OD=2.235, p=0.014) were found to be factors associated with an increased risk of GvHD. Moreover, acute GvHD symptoms were not observed in any of the recipients carrying the CCR5Delta32 allele transplanted from donors with this deletion mutation (0/11 vs. 70/151, p=0.002). INTERPRETATION AND CONCLUSION: The presence of the CCR5Delta32 allele in recipients constituted an independent and protective factor associated with a decreased risk of GvHD. This protective effect of the CCR5 deletion mutation was particularly marked in patients transplanted from donors also carrying the CCR5Delta32 allele.

Acute Disease↗
PubMed2005

HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease.

BACKGROUND: A number of genetic polymorphisms have been shown to be associated with the outcome after allogeneic hematopoietic stem-cell transplantation (HSCT). In the present study, HSP70-hom polymorphism (+2763 G/A) was analyzed in the patients and donors of allogeneic HSCT in relation to transplantation outcome, susceptibility for generation of severe toxic lesions, and acute (a) graft-versus-host disease (GVHD). METHODS: One hundred thirty-three recipients of allogeneic hematopoietic stem cells and 64 haploidentical and matched unrelated donors were investigated. All these individuals were typed for dimorphism within the HSP70-hom gene (+2763 G/A) with the use of amplification refractory mutation system technique. RESULTS.: Patients with the HSP-AA homozygous genotype presented more frequently with grade II to IV toxic lesions (12 of 14 vs. 61 of 105, P = 0.039) and aGVHD (12 of 16 vs. 56 of 114, P = 0.045). Conversely, DRB1*11 was associated with a lower risk of aGVHD manifestation (10 of 31 vs. 58 of 99, P = 0.009). These contrary associations of HSP-AA and DRB1*11 with the risk of aGVHD were confirmed using logistic regression modeling in multivariable analysis (HSP-AA, odds ratio [OR] = 3.833, P = 0.004; DRB1*11, OR = 0.224, P = 0.048). None of donor HSP genotypes or patient-donor incompatibility within HSP alleles was associated with susceptibility to toxic complications or aGVHD. CONCLUSIONS: Polymorphism of the HSP70-hom gene is associated with the development of posttransplant complications. Recipient HSP-AA homozygous genotype is a risk factor for aGVHD.

Acute Disease↗
PubMed2005

IL-6 and IL-10 promoter gene polymorphisms of patients and donors of allogeneic sibling hematopoietic stem cell transplants associate with the risk of acute graft-versus-host disease.

The present study aimed to determine existing associations between single nucleotide polymorphisms within the promoters of interleukin (IL)-6 (-174 G/C) and IL-10 (-1082 G/A, -819 C/T, -592 C/A) genes and the outcome of allogeneic sibling hematopoietic stem cell transplantation. Ninety-three recipients and 74 donors were typed for IL-6 and IL-10 alleles by polymerase chain reaction-sequence specific primer. Then, IL-6 activity in patient serum and the concentration of C-reactive protein were analyzed at various times after transplantation in relation to transplant complications and IL-6 genotype. IL-6 activity in serum was significantly higher in patients who died as a result of toxic complications and after the 6 weeks after transplantation in patients with severe acute graft-versus-host disease (aGVHD). Recipient IL-6 G genotype was associated with increased IL-6 activity and C-reactive protein production. In univariate analyses, recipient IL-6 G and donor IL-6 GG associated or tended to associate with increased risk for aGVHD. In contrast, recipient IL-10 GCC/GCC and donor IL-10 ACC decreased the risk of aGVHD. IL-6 and IL-10 polymorphic features, together with other factors known to affect the risk of aGVHD, were also subjected to multivariate analyses. These analyses confirmed the independent contribution of recipient IL-10 GCC/GCC (odds ratio = 0.085, p = 0.046) and donor IL-6 GG (odds ratio = 3.934, p = 0.034) genotypes to the risk of aGVHD.

Acute Disease↗
PubMed2005

IL-6 and IL-10 promoter gene polymorphisms do not associate with the susceptibility for multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy characterised by bone marrow infiltration and the presence of a monoclonal protein in serum and/or urine. Interleukin-6 (IL-6) has been identified as one of the most important cytokines that contributes to myeloma cell survival and proliferation. Recent investigations suggest involvement of another cytokine, IL-10, in the activation of MM cells. The present study aimed to determine whether there is an association between the polymorphic features located within the promoter regions of IL-6 and IL-10 genes and progression the disease. IL-6 (-174 G/C) and IL-10 (-1082 A/G, -819 C/T, -592 A/C) promoter single nucleotide polymorphisms (SNPs) were determined by PCR-SSP technique using commercial primers. Our single centre results were compared with the data from literature and combined in cumulative analysis employing the Mantel-Haenszel method. In univariate analysis, only IL-10 ACC genotype tended to prevail in our (Polish) group of patients. None of IL-6 genotypes or IL-10 (-1082) alleles was found to associate with MM disease either in our single centre or in cumulative study. Among patients who died within 36 months of diagnosis, a significant prevalence (P < 0.05) of IL-6 heterozygous cases as opposed to IL-6 homozygotes was observed. IL-6 and IL-10 promoter gene polymorphisms were not found to associate with the susceptibility to the development of MM. However, the IL-6 polymorphic features appeared as factors that might affect the survival of MM patients. The latter observation warrants further study.

Adult↗
PubMed2005

Recipient interferon-gamma 3/3 genotype contributes to the development of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Microsatellite polymorphism (CA)n within the first intron of the interferon- gamma gene was assessed in 160 recipients of an allogeneic hematopoietic stem cell transplant (HSCT). IFN- gamma 3/3 was found to be associated with an increased risk of chronic graft-versus-host disease (GvHD) (11/27 vs 26/133, p=0.02). Forward logistic regression analysis confirmed the role of IFN-gamma 3/3 genotype as one of the risk factors for manifestation of chronic GvHD (OR=3.180, p=0.018) together with previous acute GvHD (OR=2.752, p=0.024), cyclosporine A monotherapy (OR=2.607, p=0.029) and malignant disorders (OR=4.371, p=0.032).

Adolescent↗
PubMed2004

Combined association between IFN-gamma 3,3 homozygosity and DRB1*03 in Löfgren's syndrome patients.

In the present study, short tandem repeats (STR) polymorphism within the first intron of IFN-gamma gene in connection with HLA-DRB1*03 specificities was analysed in 43 sarcoidosis patients, 14 of which presented with Löfgren's syndrome (LS). Four out of 5 known IFN-gamma alleles with 12-15 CA repeats, respectively were detected in sarcoidosis patients. IFN-gamma 3,3 homozygosity was found to constitute a risk factor associating with LS manifestation (0.50 versus 0.19, OD = 4.18, P = 0.014). As expected, DRB1*03 prevailed in LS cases (9/14 versus 7/29, P = 0.014 LS versus non-LS cases and 9/14 versus 35/162, OD = 6.20, P = 0.001, LS patients versus controls). However, we also showed the presence of a combined association between DRB1*03 and IFN-gamma 3,3 in sarcoidosis (P = 0.017) and LS patients (P = 0.001).

Adult↗
PubMed2003

Cord blood serum affects T cells ability to produce and respond to IL-2.

The current literature suggests that cord blood (CB) cells are functionally immature. We previously reported that CB sera inhibit T cell proliferation and suggested that the microenvironment in which CB T cells reside may be, in part, responsible for their reduced function. In this study we have tried to explain some of the actions of the CB sera on peripheral blood mononuclear cells (PBMC). We showed that, as expected CB sera decreased the anti-CD3 and anti-CD28-induced proliferative response of PBMC (p < 0.01) but unexpectedly, increased the interleukin-2 (IL-2) specific proliferation of both a human T cell line (p < 0.005) and T cells within a mononuclear cell population (p < 0.05). These findings prompted us to analyse the effect of CB sera on the T cell ability to make and respond to IL-2. Stimulation of T cells in the presence of CB sera increased the frequency of IL-2 producing cells (p < 0.005) (but not the amount of IL-2 secreted) and resulted in a higher expression of CD25 (p < 0.05). Furthermore CB sera (in the presence and absence of IL-2) made the cells apoptose less (p < 0.005) than adult sera. Our results go some way to explaining the effect of the CB microenvironment on CB cellular function.

Apoptosis↗
PubMed2002

The effect of cord blood sera on CD69 expression.

We have reported previously that cord blood (CB) sera inhibit T cell proliferation and cytokine production, and have suggested that the microenvironment that CB T cells come from may be responsible for the reduced function of CB T cells. In the present study we analysed the effect of CB sera on the expression of CD69, the earliest activation marker, on T and natural killer (NK) cells. CD69 expression on adult NK cells was higher than on CB NK cells (p<0.05). CB and adult blood T cells presented with a similar proportion of CD69 expressing cells. Incubation of peripheral blood mononuclear cells (PBMC) in the CB sera enhanced CD69 expression on alloactivated T cells (p<0.05). However there was no difference in the CD69 expression within the population of alloactivated adult NK cells. Stimulation of PBMC with phytohaemagglutinin (PHA) in the presence of different sera resulted in higher CD69 expression on T cells incubated with CB sera (p<0.05), but was similar on NK cells. Our former experiments documented similar effect of CB sera on CD25 expression on mitogen and allostimulated T cells. Thus CB sera seem to have similar influences on the expression of activation markers on stimulated T cells within PBMC, implying that there may be a factor(s) within CB sera affecting lymphocyte responses and activation status.

Adult↗
PubMedDate not supplied

From molecular biology to nanotechnology and nanomedicine.

Great progress in the development of molecular biology techniques has been seen since the discovery of the structure of deoxyribonucleic acid (DNA) and the implementation of a polymerase chain reaction (PCR) method. This started a new era of research on the structure of nucleic acids molecules, the development of new analytical tools, and DNA-based analyses. The latter included not only diagnostic procedures but also, for example, DNA-based computational approaches. On the other hand, people have started to be more interested in mimicking real life, and modeling the structures and organisms that already exist in nature for the further evaluation and insight into their behavior and evolution. These factors, among others, have led to the description of artificial organelles or cells, and the construction of nanoscale devices. These nanomachines and nanoobjects might soon find a practical implementation, especially in the field of medical research and diagnostics. The paper presents some examples, illustrating the progress in multidisciplinary research in the nanoscale area. It is focused especially on immunogenetics-related aspects and the wide usage of DNA molecules in various fields of science. In addition, some proposals for nanoparticles and nanoscale tools and their applications in medicine are reviewed and discussed.

Computational Biology↗
PubMedDate not supplied

Polymorphisms within the genes encoding TNF-alpha and TNF-beta associate with the incidence of post-transplant complications in recipients of allogeneic hematopoietic stem cell transplants.

Hematopoietic stem cell transplantation (HSCT) is a curative treatment of many hematological disorders. Recent studies have shown the associations between polymorphic features of cytokine-encoding genes and the incidence of post-transplant complications in the recipients of allogeneic HSCT. This review focuses on the relationship between the polymorphic patterns of patient genes encoding tumor necrosis factor (TNF)-alpha and TNF-beta and the manifestation of post-transplant complications, acute graft-versus-host disease (aGvHD), generation of toxic lesions, and mortality. Discussed in more detail are the relationships of TNFd microsatellites and polymorphisms within the promoter region of the TNF-alpha-encoding gene (TNFA in the position (-308) and within the first intron of the TNF-beta-encoding gene (TNFB). It appeared that heterozygosity within the TNFA promoter and the first intron of the (TNFB). It gene increased the susceptibility to severe grades III-IV of toxic complications, while the presence of the TNFd3 homozygous genotype was associated with a higher risk of severe aGvHD and early mortality in patients after allogeneic HSCT. These results imply that donor-recipient genotyping, extended to cytokine loci, may be of prognostic value for transplantation outcome.

Cytokines↗