INTRODUCTION: ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR). AIM: The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children. METHODS: One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents. RESULTS: We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013). CONCLUSION: ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.

• MeSH
• bronchiální astma genetika   MeSH
• bronchiální hyperreaktivita genetika   MeSH
• dítě MeSH
• epigeneze genetická * MeSH
• genomový imprinting MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• otcové MeSH
• proteiny ADAM genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADAM33 protein, human MeSH Prohlížeč
• proteiny ADAM MeSH

BACKGROUND: ADAM33 and STAT6 belong to the candidate genes that have been commonly associated with asthma, bronchial hyperresponsiveness or IgE levels. Our objective was to assess the association of 11 SNPs of the ADAM33 and 6 of the STAT6 and their haplotypes with IgE levels and asthma. We also evaluated the possible role of parental origin of haplotypes on IgE levels. METHODS: We enrolled 109 children with asthma and 45 healthy controls. Genotyping was performed by TaqMan probes and confirmed by sequencing. Haplotype construction was based on the knowledge of parental genotypes and also inferred by using the EM algorithm and Bayes' theorem. RESULTS: None of the SNPs were associated with elevated IgE level or asthma. We found that the most frequent STAT6 haplotype ATTCAA (built from rs324012, rs324011, rs841718, rs3024974, rs3024974, rs4559 SNPs, respectively) was associated with elevated total IgE levels (P=0.01) and this haplotype was predominantly transmitted paternally (P<0.001). We compared our results with those of studies performed on German and Australian Caucasian populations and found that rs324011, rs3024974 and rs4559 SNPs in STAT6 should have a major effect on IgE levels. Therefore, we suggest the TCA haplotype alone (built from rs324011, rs3024974 and rs4559 SNPs, respectively) in STAT6 is associated with total IgE elevation. CONCLUSIONS: The influence of paternal origin of the STAT6 haplotype on IgE levels is surprising but the exact role of possible paternal imprinting in STAT6 regulation should be investigated and confirmed in future studies.

• MeSH
• bronchiální astma genetika   imunologie   MeSH
• dítě MeSH
• epigenomika * MeSH
• haplotypy MeSH
• imunoglobulin E krev   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• proteiny ADAM genetika   MeSH
• transkripční faktor STAT6 genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADAM33 protein, human MeSH Prohlížeč
• imunoglobulin E MeSH
• proteiny ADAM MeSH
• STAT6 protein, human MeSH Prohlížeč
• transkripční faktor STAT6 MeSH

Microvessels respond to metabolic stimuli (e.g. pO(2)) and hemodynamic forces (e.g. shear stress and wall stress) with structural adaptations including angiogenesis, remodeling and pruning. These responses could be mediated by differential gene expression in endothelial and smooth muscle cells. Therefore, rat mesenteric arteries and veins were excised by microsurgery, and mRNA expression of four angioadaptation-related genes was quantified by real time duplex RT-PCR in equal amounts of total RNA, correlated to two different house keeping genes (beta-actin, GAPDH). The results show higher expression of VEGFA, TIE2, and ANG2 in arteries than in veins, but equal expression of ADAMTS1. Higher availability of VEGFA mRNA in endothelial cells of arteries shown here could contribute to the maintenance of mechanically stressed blood vessels and counteract pressure-induced vasoconstriction.

• MeSH
• angiopoetin-2 genetika   MeSH
• arteriae mesentericae fyziologie   MeSH
• cévní endotel fyziologie   MeSH
• exprese genu fyziologie   MeSH
• fyziologická adaptace fyziologie   MeSH
• krysa rodu Rattus MeSH
• messenger RNA metabolismus   MeSH
• mikrocirkulace fyziologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Sprague-Dawley MeSH
• protein ADAMTS1 MeSH
• proteiny ADAM genetika   MeSH
• receptor TIE-2 genetika   MeSH
• svaly hladké cévní fyziologie   MeSH
• vaskulární endoteliální růstový faktor A genetika   MeSH
• vazokonstrikce fyziologie   MeSH
• vena mesenterica fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Adamts1 protein, rat MeSH Prohlížeč
• angiopoetin-2 MeSH
• messenger RNA MeSH
• protein ADAMTS1 MeSH
• proteiny ADAM MeSH
• receptor TIE-2 MeSH
• vascular endothelial growth factor A, rat MeSH Prohlížeč
• vaskulární endoteliální růstový faktor A MeSH

BACKGROUND: Thrombotic thrombocytopenic purpura is characterized by microvascular platelet clumping resulting in thrombocytopenia, microangiopathic hemolysis, neurological abnormality, and renal dysfunction. Similar manifestations also occur in patients with the hemolytic uremic syndrome or other types of disorders. Recent studies demonstrate that severe deficiency of the von Willebrand factor cleaving metalloprotease, ADAMTS 13, causes thrombotic thrombocytopenic purpura. Aim of our study was to characterize gene defects causing inherited type of disease. METHODS AND RESULTS: We investigated nine patients with recurrent type of disease with familiar origin and twelve relatives. Samples were taken in a remission of disease. We measured activity of ADAMTS13 (vWF-CP) with modified method of the quantitative immunoblotting of degraded vWF multimers. Mutation screening was carried out by sequencing all 29 exons and flanking intron regions of the ADAMTS13 gene. Five distinct mutations were found. Three of them are novel. CONCLUSIONS: Mutation analysis of the ADAMTS 13 gene brought interesting results in eight patients. We found a one single base frameshift insertion, 4143insA in 8 of 9 unrelated individuals. This investigation represents an advantage in the differential diagnosis of disease since the thrombotic thrombocytopenic purpura phenotype in childhood can be variable and rapid detection of mutation is helpful for the recurrence prevention.

• MeSH
• dítě MeSH
• lidé MeSH
• mutace MeSH
• posunová mutace MeSH
• protein ADAMTS13 MeSH
• proteiny ADAM genetika   MeSH
• trombotická trombocytopenická purpura genetika   MeSH
• von Willebrandův faktor genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADAMTS13 protein, human MeSH Prohlížeč
• protein ADAMTS13 MeSH
• proteiny ADAM MeSH
• von Willebrandův faktor MeSH