BACKGROUND: Chronic venous disease (CVD) is a common disorder of lower extremities. OBJECTIVES: The study was scheduled to investigate the relationship between polymorphisms in major proinflammatory genes TNF α (-238 A/G; -308 A/G), TNF β (NcoI), IL-1β (+3953 T/C); IL-6 (-174 G/C; -596 G/C) and ADAM17 (3'TACE) and CVD risk. Genotype-phenotype study was calculated to test possible association between examined genotypes and phenotypes of CVD. METHODS: Finally, 150 CVD patients and 227 control subjects were enrolled to the study. Genotypes in proinflammatory gene polymorphisms were identified from isolated DNA by PCR method and restriction analysis. RESULTS: Significant differences in genotype distribution/allelic frequencies in TNF β gene, IL-1 β gene and in ADAM17 gene polymorphisms were found between CVD women and control ones. In the genotype-phenotype study, identified genotypes were associated with arterial hypertension (ADAM17, IL-6-men), ischaemic heart disease (TNF α and β genes), diabetes mellitus (ADAM17-women, TNF β-men), age of CVD onset (TNF α and IL-6), ulceration (ADAM17), duration of ulceration (ADAM17), ulceration recurrence (ADAM17-women), home care necessity (TNF α), varices surgery (TNF α), erysipelas development (ADAM17-men) and tumour development (TNF α). CONCLUSION: Studying of these polymorphisms associations can help us better identify patients at higher risk of developing severe CVD.

• MeSH
• chronická nemoc MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• interleukin-1beta genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kardiovaskulární nemoci * genetika   MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• protein ADAM17 genetika   MeSH
• TNF-alfa * genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The aim of this study was to investigate possible associations of the five DNA polymorphic genotypes in the HLA region (transporter associated with antigen processing [TAP1; TAP1 333 a/b, TAP1 637 c/d], the HLA-DRB1*1501-rs3135388, tumor necrosis factor [TNF]α [-238 G/A] and NcoI TNFβ) with characteristics of family history in patients with psoriasis vulgaris. MATERIALS AND METHODS: A total of 201 Czech patients with psoriasis were enrolled in the study. The patients were genotyped for the five common polymorphisms in TAP1, TNFα, and TNFβ genes (6p21.3) using the polymerase chain reaction-restriction fragment length polymorphism-based methodology. RESULTS: We observed significantly higher prevalence of Ile333Ile TAP1 allele in patients whose first-degree relatives had a positive family history of psoriasis (Pa = 0.04). No differences related to family history of psoriasis were observed in HLA-DRB1*1501 polymorphism. As for the TNFα (-238 G/A) polymorphism, a significant increase of the GG genotype was observed in patients, especially men with second- and third-degree relatives with psoriasis (Pg = 0.008). Similarly, the B2B2 genotype of NcoI TNFβ polymorphism was more frequent in psoriatic patients, especially women, whose second- and third-degree relatives had psoriasis (Pg = 0.004). Finally, the haplotype analysis of all five polymorphisms revealed that the frequency of haplotype bcCB1A was different between not only men and women with psoriasis (P = 0.007) but also between men and women without a family history of psoriasis (P = 0.007). CONCLUSIONS: Haplotype association of HLA gene polymorphisms with genealogy aspects of psoriasis facilitates a better understanding of etiopathogenetic aspects of the diseases.

• MeSH
• ABC transportéry genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci epidemiologie   genetika   MeSH
• haplotypy MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus genetický MeSH
• psoriáza epidemiologie   genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• TNF-alfa genetika   MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of the study is to assess the association of four mostly discussed candidate genes (connexin 37, plasminogen activator inhibitor -1, stromelysin-1 and lymfotoxin-alfa) with acute coronary syndroms and their sequales. Candidate genes under study will be evaluated in 2000-2500 patients with acute coronary syndromes admitted to Coronary Care unites and in the representative sample of the Czech population (n=2600)in cross-sectional study and in prospective study. This project should evaluate the effect of genetical determination on the incidence of acute coronary syndromes and their acute and late complications.

Cílem projektu je stanovit úlohu čtyř nejvíce diskutovaných kandidátních genů (connexin 37, inhibitor tkáňového aktivátoru 1, stromelysin-1 a lymfotoxin alfa) na výskyt a komplikace akutních koronárních syndromů v české populaci. Sledované kandidátní geny budou stanoveny u pacientů s akutním koronárním syndromem (n=2000-2500) a u reprezentativního vzorku české populace. Úloha těchto kandidátních genů bude hodnocena jednak průřezově, jednak prospektivně po 12měsíčním sledování. Navrhovaná studie by mělastanovit vliv genetické determinace na výskyt a komplikace koronárních příhod ve vysoce rizikové české populaci na rozsáhlém a neselektovaném vzorku pacientů s koronárními syndromy.

• MeSH
• akutní nemoc MeSH
• genetické asociační studie MeSH
• infarkt myokardu genetika   MeSH
• inhibitor aktivátoru plazminogenu 1 analýza   MeSH
• konexiny analýza   MeSH
• koronární nemoc genetika   komplikace   MeSH
• lymfotoxin-alfa analýza   MeSH
• matrixová metaloproteinasa 3 analýza   MeSH
• polymerázová řetězová reakce metody   využití   MeSH
• populace genetika   MeSH
• prospektivní studie MeSH
• průřezové studie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• biologie
• kardiologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

The majority of acute coronary syndrome (ACS) cases cannot be explained by the analysis of commonly recognized risk factors; thus, the analysis of possible genetic predispositions is of interest. The genes for connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 (PAI-1) and lymphotoxin-alpha are among many presently known candidate genes that are associated with risk factors for ACS.OBJECTIVE:To identify the potential impact of the functional variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha on ACS in a Caucasian Czech population. METHODS:A total of 1399 consecutive patients (1016 men and 383 women) with ACS from five coronary care units located in Prague (Czech Republic) were analyzed; a representative sample of 2559 healthy individuals (1191 men and 1368 women) were also genotyped and served as controls. RESULTS:The gene variants analyzed were not significantly associated with the prevalence of ACS or the classical risk factors of ACS development such as high plasma lipid levels, hypertension, diabetes, high body mass index or smoking. CONCLUSION:In a Caucasian Czech population sample, genetic variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha were not significantly associated with a predisposition toward ACS.

• MeSH
• akutní koronární syndrom * genetika   MeSH
• genetická predispozice k nemoci MeSH
• konexiny * MeSH
• lidé MeSH
• lymfotoxin-alfa * MeSH
• matrixová metaloproteinasa 3 * MeSH
• polymorfismus genetický * MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Human renal epithelial cells might play an important role during the allograft rejection by producing chemokines in response to proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta produced by endothelial and epithelial cells early after transplantation. The production of chemokines allows inflammatory cells to be drawn into the kidney graft and therefore plays a critical role in the pathophysiologic processes that lead to the rejection of renal transplant. In this process, two chemokine superfamilies, the CC and the CXC chemokines, are the most important. The CC chemokines target mainly monocytes and T lymphocytes, while most of the CXC chemokines attract neutrophils. We showed in our study that in vitro, in unstimulated cells, basal mRNA expression of CXC chemokines (Groalpha, Grobeta, Grogamma, ENA-78 and GCP-2, IL-8) that attract neutrophils was detectable and expression of these genes and chemokine release were increased in TNF-alpha- and IL-1beta-induced renal epithelial cells. Most of the CC chemokines [monocyte chemotactic protein-1 (MCP-1), macrophage Inflammatory protein 1 beta (MIP-1beta), regulated upon activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP-3alpha)] showed detectable mRNA expression only after stimulation with proinflammatory cytokines and not in control cells. TNF-alpha seems to induce preferably the expression of RANTES, MCP-1, interferon-inducible protein (IP-10) and Interferon-Inducible T-cell Alpha Chemoattractant (I-TAC), while IL-1beta induces mainly IL-8 and epithelial neutrophil-activating peptide 78 (ENA-78).

• MeSH
• chemokiny CC biosyntéza   genetika   imunologie   MeSH
• chemokiny CXC biosyntéza   genetika   imunologie   MeSH
• cytokiny biosyntéza   farmakologie   imunologie   MeSH
• ELISA MeSH
• epitelové buňky imunologie   MeSH
• interleukin-1beta farmakologie   imunologie   MeSH
• interleukin-8 biosyntéza   genetika   imunologie   MeSH
• ledviny imunologie   MeSH
• lidé MeSH
• lymfotoxin-alfa farmakologie   imunologie   MeSH
• messenger RNA biosyntéza   genetika   MeSH
• nádorové buněčné linie MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• rejekce štěpu genetika   imunologie   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• transplantace ledvin imunologie   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: Lactate levels after cardiac surgery are influenced by different proinflammatory (TNF, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines. The goal of the study was to determine the relationship between polymorphism in the IL-10 (-1082G/A) and TNF-beta (+252G/A) genes and lactate levels in patients after cardiac surgery. METHODS: We performed prospective observational study in 168 consecutive adult patients without left ventricle dysfunction undergoing elective coronary artery bypass grafting. Lactic acid levels were documented at five different time points: 10 min after beginning of cardiopulmonary bypass, 40 min after cardiopulmonary bypass termination, and 30 min, 8h, and 16 h after the surgery. Genetic analysis for polymorphism was performed by mismatched polymerase chain reaction and restriction analysis. RESULTS: No association was found between single polymorphism in IL-10 or TNF-beta gene and lactate levels, but the carriers of IL-10/TNF-beta genotype combination +A/GG had significantly different course of lactate levels in time with decrease in lactate (in comparison with increase in other groups) at 8h after the surgery. CONCLUSIONS: IL-10 (-1082G/A) and TNF-beta (+252G/A) gene polymorphisms have a little, yet measurable influence on the time course of changes in lactate levels after cardiac surgery.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• frekvence genu MeSH
• funkce levé komory srdeční MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• interleukin-10 genetika   MeSH
• koronární bypass MeSH
• kyselina mléčná krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• mediátory zánětu krev   MeSH
• polymorfismus genetický MeSH
• pooperační období MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

OBJECTIVE: A role of autoreactive T cells for type 1 diabetes pathogenesis is considered crucial. In our pilot study we addressed if autoreactive mononuclear cells are present also in peripheral blood of patients with other specific forms of diabetes as cystic fibrosis related diabetes (CFRD). METHODS: Cellular immune responses to a known beta-cell autoantigen (GAD65 and GAD65 derived peptides) were analysed by ELISPOT (IFN-gamma) and by protein microarray analysis in four patients suffering from CFRD, in four cystic fibrosis (CF) patients without diabetes, in eight type 1 diabetes patients (without CF) and in four healthy controls. RESULTS: Response to the autoantigen GAD65 (protein and peptides) was observed in 7/8 patients suffering from CF and in all type 1 diabetes patients. Post-stimulation production of Th1 cytokines (IFN-gamma, TNF-beta) was observed in 2/4 CFRD, 1/4 CF patients and in 7/8 type 1 diabetes patients. All these patients carry prodiabetogenic HLA-DQ genotype. Th2- and Th3 type of cytokine pattern was observed in 2/4 CF patients. Production of IL-8 was observed in the third CFRD as well as in the third CF patient and in 1/8 type 1 diabetes patient and borderline production of this chemokine was also observed in 2/4 healthy controls. No reaction was observed in the other 2/4 healthy controls and in the fourth CFRD patient who carried a strongly protective genotype and did not produce autoantibodies. The most potent peptide of GAD65 was amino acids 509-528. CONCLUSIONS: We consider our observations as a sign of a reaction directed against the self-antigen GAD65 that are closely connected to type 1 diabetes. In CF patients who do not develop diabetes autoreactive mechanisms are very probably efficiently suppressed by immune self-tolerance mechanisms. CFRD patients are a heterogenic group. To disclose those who may display features of autoimmune diabetes could have an impact for their therapy and prognosis.

• MeSH
• autoprotilátky imunologie   krev   MeSH
• čipová analýza proteinů MeSH
• cystická fibróza imunologie   komplikace   MeSH
• diabetes mellitus etiologie   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• financování organizované MeSH
• glutamát dekarboxyláza imunologie   MeSH
• HLA-DQ antigeny imunologie   MeSH
• interferon gama krev   MeSH
• interleukin-8 krev   MeSH
• izoenzymy MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé MeSH
• lymfotoxin-alfa krev   MeSH
• mladiství MeSH
• pilotní projekty MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• HLA-DR antigeny genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• plicní sarkoidóza genetika   MeSH
• tumor nekrotizující faktory genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

• MeSH
• adenin MeSH
• finanční podpora výzkumu jako téma MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• parodontitida genetika   MeSH
• polymorfismus genetický genetika   MeSH
• tumor nekrotizující faktory genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• lipidy krev   MeSH
• lymfotoxin-alfa genetika   MeSH
• metabolismus lipidů MeSH
• polymorfismus genetický MeSH
• restrikční endonukleasy typu II MeSH
• tumor nekrotizující faktory genetika   MeSH
• Check Tag
• lidé MeSH