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Role of peripheral blood monocytes and innate immunity in diabetes
Zinková, Alžběta ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Introduction: Diabetes mellitus is a polygenic disease and its development is influenced to some extent by environmental factors as well. Innate immunity triggers nonspecifically first defense reactions after penetration of the pathogen into the body, while overstimulation components of innate immunity may give rise to autoimmune diseases, including diabetes type 1. The components of innate immunity are, among others, Toll-like receptors (TLRs) belonging to a group of the structures recognizing preserved molecular structures characteristic of pathogens. Toll-like receptors are abundantly expressed by monocytes which produce prolactin (PRL) having an immunostimulatory function. To clarify the role of innate immunity in the pathogenesis of diabetes, we focused on the expression of mRNA and protein expression of TLR2 and TLR4. The expression of PRL was studied only at the level of mRNA. Monocytes were separated by flow cytometry into classical (CD14++) and nonclassical (CD14+). We monitored their percentages and the degree of expression of CD14 antigen on their surface.The operational objective of this dissertation was to optimize the stimulation of monocytes for the planned study of the function of non-pituitary prolactin in vitro and determine the appropriateness of the use of healthy donors' buffy...
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Genetic study of obesity in children
Říhová, Aneta ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Obesity is multifactorial dissease. Genetics factors participate in its origin of 40-70% (Barsh et al., 2000). Incidence of obesity is associated with a number of complications, which affect quality of life and abbreviate its length. It is projected in constantly younger age and its prevalence in the world grows. Even though several hundred genetics markers associated with obesity have been described, we still do not know all causes, which complicates efficiancy of treatment. Subject of this study was research of selected genes and their polymorphisms: FABP2 (rs1799883) and PLIN (rs1052700 and rs894160). The aim was to establish association between genotypes and antropometric and biochemical parameters related to obesity in group of 299 children and adolescents aged 7-18 years. Next goal was to establish whether these polymorphisms affect success of reduction therapy. SNP associations with antropometric and/or biochemical parameters were evaluated for boys and girls separately. Observed genotype frequencies between sex did not differ and they were in accordance with those explored in other populations. In rs1799883 polymorphism neither association with measured anthropometric and biochemical parameters nor effect on weight loss during reduction therapy have been found. The TT homozygote subjects of...
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Association of HSP70 genes with idiopathic inflammatory myopathy in a homogeneous cohort of Czech patients
Svitálková, Táňa ; Novota, Peter (advisor) ; Daňková, Pavlína (referee)
MHC complex is the most polymorphic, most complex and one of the most important parts of a genome which takes a part in the immunity response of an organism. In a human body, it is tagged as HLA (human leukocyte antigen) and consists of 224 genes. HLA genes are associated as a risk factor in numerous autoimmunity diseases. One of systemic autoimunity diseases is idiopathic inflammatory myopathy. It is a disease with a clinical manifestation of a chronical muscle inflammation with a destruction of own cells and leading to a damage of the whole organs. IIM involves several diagnoses - polymyopathy (PM), dermathomyopathy (DM) myopathy associated with tumor diseases (CDM) myopathy with inflammatory inclusion corps (IBM) and others. MHC complex consists of three parts, two of which - MHC class I and II - are already examined rather well and have been associated with numerous (mainly autoimmunity) diseases. Last part of MHC is located between class I and II is an area of around 150 genes called "non Class I/II" (Remáková, Novota, 1999). The main subject for my thesis are three genes of the HLA complex in which has been proven a function in regulation mechanism of some autoimmunity diseases. These genes play a part in the immunity response, because they are able to stimulate the adaptive and native...
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Regulation of gene expression of HSP70 genes and its dependence on the genotype of HSP70 genes.
Ambrož, Antonín ; Novota, Peter (advisor) ; Kotrbová - Kozak, Anna Katarzyna (referee)
The topic of the presented thesis is the regulation of gene expression level of the three HSP70 genes in mononuclear cells. We investigated the dependence of expression regulation (induction) abiliy on selected point mutations, so-called SNPs (single nucleotide polymorphism) in the observed genes. The mononuclear cells were obtained from peripheral blood samples of healthy individuals. In order to analyze their gene expression, we selected individuals who were homozygous for at least one of the monitored point mutations. Taking into account the chosen criteria for healthy individuals we based on interviews with these individuals and their personal history. We determined the polymorphisms observed in two cell stress-inducible HSP70-1 (HSPA1A) and HSP70-2 (HSPA1B) genes and in one constitutively expressed gene HSP70-Hom (HSPA1L). Further, we have analyzed HSP70s gene expression regulation and the relation between the expression regulation and studied polymorphisms. We determined the degree of regulation of a gene expression in the studied genes in relation to two SNPs -110A/C (rs1008438), +190G /C (rs1043618) gene HSP70-1, and two SNPs +1267A/G (rs1061581), +2074G /C (rs539689 ) of the HSP70-2 gene, and the mutation of one five-nucleotide (rs9281590) HSP70-2 gene, and one SNP +2437T/C (rs2227956) of...
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Population differences in the distribution of HLA-B27 allele in ankylosing spondylitis
Lennerová, Tereza ; Hušáková, Markéta (advisor) ; Novota, Peter (referee)
Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting mainly the spine and the sacroiliac joints. This disorder has a genetic background and is strongly associated with HLA-B27 gene which occurs in about 90 % of patients. The prevalence of ankylosing spondylitis usually correlates with the frequency of HLA-B27. The strength of association HLA-B27 with AS varies between different populations and is also distinct for individual alleles of HLA-B27 gene. Some alleles can increase a risk of ankylosing spondylitis while others may have a protective effect. This work deals with the population differences in the occurrence of HLA-B27 alleles and their relation to development of ankylosing spondylitis. Key words: ankylosing spondylitis, HLA-B27, allele, subtype, population differences
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Expression profiles of selected celiac disease candidate genes
Okruhlicová, Šárka ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Introduction: Celiac disease is a multifactorial autoimmune disease that is caused by a response to gluten and related proteins in genetically susceptible individuals. Genetic studies have demonstrated a high association of celiac disease with HLA genes (human leukocyte antigens) II. Class. Approximately 90-95% of the patients have a HLA-DQ2 haplotype (DQA1*05/DQB1*02), the remaining 5-10% are carriers of HLA-DQ8 (DQA1*03/DQB1*03) or inherited only one allele of HLA-DQ2 genotype. Approximately 30% of the healthy population has this haplotype and only 1% develops celiac disease. If 30% of healthy individuals have this haplotype and do not develop celiac disease, this may be affected by a different level of expression in healthy and diseased individuals. Aims: The aim was to design and test a primer and probe system for QPCR that will amplify all selected HLA-DQA1 and HLA-DQB1 candidate genes at risk for celiac disease and use this system to measure the relative level of expression of risk genes in healthy donors and patients with celiac disease. Methods: The study included 10 patients with recent celiac disease and 15 healthy donors who were selected from the database of the Institute of Medical Genetics of the 3.LF UK based on their genotypes HLA-DQA1 and HLA-DQB1. Patients were first detected...
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Expression profiles of selected celiac disease candidate genes
Okruhlicová, Šárka ; Daňková, Pavlína (advisor) ; Novota, Peter (referee)
Introduction: Celiac disease is a multifactorial autoimmune disease that is caused by a response to gluten and related proteins in genetically susceptible individuals. Genetic studies have demonstrated a high association of celiac disease with HLA genes (human leukocyte antigens) II. Class. Approximately 90-95% of the patients have a HLA-DQ2 genotype (DQA1 * 05 / DQB1 * 02), the remaining 5-10% are carriers of HLA-DQ8 (DQA1 * 03 / DQB1 * 03) or inherited only one allele of HLA-DQ2 genotype. Approximately 30% of the healthy population has this genotype and only 1% develops celiac disease. If 30% of healthy individuals have this genotype and do not develop celiac disease, this may be affected by a different level of expression in healthy and diseased individuals. Aims: The aim was to design and test a primer and probe system for QPCR that will amplify all selected HLA-DQA1 and HLA-DQB1 candidate genes at risk for celiac disease and use this system to measure the relative level of expression of risk genes in healthy donors and patients with celiac disease. Methods: The study included 10 patients with recent celiac disease and 15 healthy donors who were selected from the database of the Institute of Medical Genetics of the 3.LF UK based on their genotypes HLA-DQA1 and HLA-DQB1. Patients were first...
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Population differences in the distribution of HLA-B27 allele in ankylosing spondylitis
Lennerová, Tereza ; Hušáková, Markéta (advisor) ; Novota, Peter (referee)
Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting mainly the spine and the sacroiliac joints. This disorder has a genetic background and is strongly associated with HLA-B27 gene which occurs in about 90 % of patients. The prevalence of ankylosing spondylitis usually correlates with the frequency of HLA-B27. The strength of association HLA-B27 with AS varies between different populations and is also distinct for individual alleles of HLA-B27 gene. Some alleles can increase a risk of ankylosing spondylitis while others may have a protective effect. This work deals with the population differences in the occurrence of HLA-B27 alleles and their relation to development of ankylosing spondylitis. Key words: ankylosing spondylitis, HLA-B27, allele, subtype, population differences
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