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National Repository of Grey Literature 3 records found  Search took 0.00 seconds. 
Epigenetic regulation of HLA class II genes and their role in autoimmune diseases.
 Čepek, Pavel ; Kotrbová - Kozak, Anna Katarzyna (advisor) ; Horníková, Lenka (referee)
Abstract Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Its incidence in Europe is continuously rising. The highest T1D risk is associated with HLA (human leukocyte antigen) class II genes. HLA class II molecules play a key role in regulation of immune response. They contribute to the selection of T cell repertoire by presenting antigenic peptides to the CD4+ T lymphocytes. HLA class II expression is controlled by regulatory module that is situated 150 - 300 base pairs upstream of the transcription- initiation site in all HLA class II genes. Polymorphisms in this region are linked to some autoimmune diseases. There were identified several promoter alleles (named QAP) in the HLA DQA1 gene promoter region. Most of the polymorphisms appear to be conserved within haplotype. Individual QAP alleles may have a different promoter strength by which they influence expression of HLA DQA1 gene alleles. Promoter strength can be modulated by DNA methylation. Aims:Our aim was to define methylation profile of HLA DQA1 promoters and determine the mRNA expression of individual alleles of HLA DQA1 gene in T1D patients. The mRNA expression level of HLA DQA1 gene alleles was determined using quantitative PCR. Methods: 30 diabetic pacients (age range 21 to 76 years), were included in this pilot...
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Epigenetic regulation of HLA class II genes and its modification during the lifetime
 Lamborová, Věra ; Kotrbová - Kozak, Anna Katarzyna (advisor) ; Černý, Jan (referee)
Background: The major histocompatibility complex (MHC) molecules play an important role in the immune response regulation and in the maintenance of the immune homeostasis. Regulation of their expression is therefore a key factor influencing the adaptive immune response. DNA methylation of gene regulatory regions is one of the mechanisms of gene expression control that affects the accessibility of DNA to transcription factors. Ageing is connected with changes in DNA methylation and increased predisposition to autoimmune diseases in older age could be associated with changes in MHC class II genes methylation. Aims: The aim of this diploma thesis is to analyze the methylation profile of DQA1 and DQB1 genes regulatory regions and to compare its differences between the generations and between individual alleles. The next aim is to compare DQA1 mRNA expression between the generations and between single alleles. Methods: DNA and RNA were isolated from blood of three age group donors. DNA was converted by the bisulfite treatment and regulatory regions of HLA class II genes were amplified and cloned into bacteria. Positive clones were sequenced and then analyzed. RNA was reverse transcribed and its expression level was determined by real-time PCR. Results: Statistically significant differences were found by...
Detailed record
Epigenetic regulation of HLA class II genes and their role in autoimmune diseases.
 Čepek, Pavel ; Kotrbová - Kozak, Anna Katarzyna (advisor) ; Horníková, Lenka (referee)
Abstract Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease. Its incidence in Europe is continuously rising. The highest T1D risk is associated with HLA (human leukocyte antigen) class II genes. HLA class II molecules play a key role in regulation of immune response. They contribute to the selection of T cell repertoire by presenting antigenic peptides to the CD4+ T lymphocytes. HLA class II expression is controlled by regulatory module that is situated 150 - 300 base pairs upstream of the transcription- initiation site in all HLA class II genes. Polymorphisms in this region are linked to some autoimmune diseases. There were identified several promoter alleles (named QAP) in the HLA DQA1 gene promoter region. Most of the polymorphisms appear to be conserved within haplotype. Individual QAP alleles may have a different promoter strength by which they influence expression of HLA DQA1 gene alleles. Promoter strength can be modulated by DNA methylation. Aims:Our aim was to define methylation profile of HLA DQA1 promoters and determine the mRNA expression of individual alleles of HLA DQA1 gene in T1D patients. The mRNA expression level of HLA DQA1 gene alleles was determined using quantitative PCR. Methods: 30 diabetic pacients (age range 21 to 76 years), were included in this pilot...
Detailed record

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