Sarcoidosis is a granulomatous disorder showing a clear association with MHC (HLA) class I and class II genes. In order to investigate whether polymorphisms of nearby pro-inflammatory genes located within the MHC class III region may also contribute to susceptibility to sarcoidosis or to its clinical manifestation, tumour necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were chosen for analysis in a case-control association study. In order to evaluate the findings on the TNF-alpha and LT-alpha genes in connection with the closely linked MHC class II region, 'classical' HLA-DRB1 locus was also investigated. Polymerase chain reaction-based methodologies were used in order to characterize two single-nucleotide polymorphisms (TNF-308*G/A and LTAlpha+252*A/G) and HLA-DRB1 allele groups in 114 Czech patients with pulmonary sarcoidosis and 425 healthy controls. LTA+252*G and HLA-DRB1*13 allele carriers were more frequent in patients, compared to those in controls. By contrast, HLA-DRB1*07 carriers were less frequent among sarcoidosis patients. The overrepresentation of TNF-308*A, LTAlpha+252*G and HLA-DRB1*03 allele carriers was found in a subgroup of sarcoidosis patients presenting with Lofgren's syndrome (LS) by comparison with the subgroup of patients without LS (NLS; phenotype frequency LS vs NLS: 68.8 vs 37.1% for TNF-308*A, 93.8 vs 66.3% for LTA+252*G and 68.8 vs 21.3% for DRB1*03). The data suggest that the LTAlpha and HLA-DRB1 genes themselves or a gene located nearby contributes to the susceptibility to sarcoidosis and that TNF-308*A, LTA+252*G and HLA-DRB1*03 alleles are associated (directly or via linkage with unknown causative locus) with LS as a specific manifestation of the disease.

• MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• HLA-DR antigeny genetika   MeSH
• HLA-DRB1 řetězec MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• mladiství MeSH
• plicní sarkoidóza komplikace   genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• syndrom MeSH
• TNF-alfa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HLA-DR antigeny MeSH
• HLA-DRB1 řetězec MeSH
• lymfotoxin-alfa MeSH
• TNF-alfa MeSH

OBJECTIVES: Matrix metalloproteinase-1 (MMP-1) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of chronic periodontitis. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the MMP-1 gene and chronic periodontitis susceptibility and/or severity in a Czech population. MATERIALS AND METHODS: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe chronic periodontitis and 196 unrelated control subjects. MMP-1 promoter polymorphisms (-1607 1G/2G, -519A/G, and -422A/T) were genotyped using standard polymerase chain reaction-restriction fragment length product methods. RESULTS: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the -519A/G and -422A/T variants between periodontitis and control groups. However, a trend to increased frequency of the -1607 1G allele was observed in patients with chronic periodontitis compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with chronic periodontitis among non-smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the MMP-1 -422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017). CONCLUSIONS: Our results demonstrate that the polymorphisms in the MMP-1 promoter may have only a small effect on the etiopathogenesis of chronic periodontitis.

• MeSH
• alely MeSH
• chronická nemoc MeSH
• dospělí MeSH
• epidemiologické metody MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 1 genetika   MeSH
• parodontitida enzymologie   genetika   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický genetika   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• matrixová metaloproteinasa 1 MeSH

BACKGROUND: Several findings suggest that nitric oxide (NO) plays a significant role in the regulation of the Th1/Th2 balance and contributes to the development of allergic diseases. Our study investigates a possible association of C/T transition located 276-bp downstream from the translation termination site in exon 29 of the human nitric oxide synthase type 1 (NOS1) gene with immunoglobulin E (IgE)-mediated allergic diseases in the Czech population. METHODS: The study included 688 subjects - 368 patients with clinically manifested allergic diseases and 320 unrelated controls with negative familial history of asthma/atopy. The NOS1 genotypes were determined by polymerase chain reaction (PCR) and restriction analysis by Eco72I. RESULTS: No significant differences were found for allele or genotype frequencies of the 5266 C/T polymorphism in exon 29 of the NOS1 gene between IgE-mediated allergic diseases (or asthma alone) and healthy subjects. However, this common polymorphism showed a significant association with signs of atopy, especially with total serum IgE levels [log(e) IgE levels (mean +/- SD): CC genotype = 4.34 +/- 1.40; CT genotype = 4.58 +/- 1.53; TT genotype = 5.01 +/- 1.61; P < 0.05). CONCLUSIONS: Our findings suggest that NOS1 gene may participate in the pathogenesis of high total serum IgE levels in allergic diseases in our population. These findings provide support for NOS1 as a candidate gene for IgE-mediated allergy.

• MeSH
• alely MeSH
• alergie krev   genetika   imunologie   MeSH
• cytosin MeSH
• dospělí MeSH
• frekvence genu MeSH
• genotyp MeSH
• imunoglobulin E krev   imunologie   MeSH
• lidé MeSH
• mladiství MeSH
• polymorfismus genetický * MeSH
• studie případů a kontrol MeSH
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého genetika   MeSH
• thymin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cytosin MeSH
• imunoglobulin E MeSH
• NOS1 protein, human MeSH Prohlížeč
• synthasa oxidu dusnatého, typ I MeSH
• synthasa oxidu dusnatého MeSH
• thymin MeSH

The aim of the study was to assess the association between promoter polymorphism [A(-596)G] in interleukin-6 gene and office systolic and diastolic blood pressures, and the heart rate (HR) in apparently healthy Czech subjects. Furthermore, we evaluated the possible influence of gender, BMI and smoking on these supposed associations. An age-matched (40-50 years) and gender-matched (F/M=81/89) sample of apparently healthy Czech subjects (n=170, F/M=81/89) without hypertension, other cardiovascular diseases or diabetes was examined. The A(-596)G Il-6 gene polymorphism was detected by the PCR method. No differences in genotype distribution and/or allelic frequency was found between groups with lower systolic blood pressure (Ł 122 mm Hg) and higher systolic blood pressure (> 122 mm Hg). Similarly, no differences in the IL-6 polymorphism were found between lower (Ł 86 mm Hg) and higher (> 86 mm Hg) diastolic blood pressure groups. However, we proved a significant increase of genotypes AG+GG as well as the allele (-596)G in higher (>78 beats/min) heart rate group. The genotypes AG+GG represent significantly higher relative risk for higher HR frequency, especially in women. Among lean persons with a low heart rate frequency, fewer AG+GG genotypes were determined than among any other subjects. The genotypes AG+GG are more frequent in non-smoking persons with higher HR compared to non-smoking subjects with lower HR, especially in women. Gender, BMI and smoking substantially modify the distribution of A(-596)G Il-6 gene polymorphism in apparently healthy persons with lower or higher heart rate.

• MeSH
• alely MeSH
• dospělí MeSH
• elektroforéza v polyakrylamidovém gelu metody   MeSH
• frekvence genu MeSH
• genotyp MeSH
• index tělesné hmotnosti MeSH
• interleukin-6 genetika   MeSH
• kouření škodlivé účinky   MeSH
• krevní tlak genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymerázová řetězová reakce metody   MeSH
• polymorfismus genetický * MeSH
• promotorové oblasti (genetika) genetika   MeSH
• sexuální faktory MeSH
• srdeční frekvence genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• interleukin-6 MeSH

BACKGROUND: Immunoglobulin E (IgE)-mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations. METHODS: We investigated relationship among atopic phenotypes and two polymorphisms [C(-159)T and G(-1359)T] in the promoter of the CD14 gene in the Czech population. Polymerase chain reaction with restriction fragment length polymorphism analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n = 562) and random controls (n = 320). RESULTS: The CD14 allele or genotype distributions were similar in patients and control group. However, the frequency of the C allele of the C(-159)T polymorphism was higher in patients with positive skin prick tests for moulds than in patients without reactivity to this antigen (P < 0.002, Pcorr<0.01). In addition, we found that patients with homozygous genotype (GG) of the G(-1359)T polymorphism had marginally lower percentage of positive skin prick tests compared with the other genotypes (P < 0.029, Pcorr > 0.05). CONCLUSIONS: Our study supports the idea that CD14 gene variants may act as disease modifiers of IgE-mediated allergic diseases.

• MeSH
• alergeny krev   imunologie   MeSH
• anafylaxe krev   imunologie   MeSH
• antigeny CD14 genetika   MeSH
• bronchiální astma diagnóza   genetika   imunologie   MeSH
• časná přecitlivělost diagnóza   genetika   imunologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• imunoglobulin E imunologie   MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• promotorové oblasti (genetika) MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• alergeny MeSH
• antigeny CD14 MeSH
• imunoglobulin E MeSH

We tested the capabilities of drugs elevating extracellular adenosine and of granulocyte colony-stimulating factor (G-CSF), given alone or in combination, to mobilize haematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) and granulocytes into peripheral blood. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP) serving as an adenosine prodrug. DP + AMP, G-CSF or all these drugs in combination were administered either singly or repeatedly in a 4-d treatment regimen. Elevation of extracellular adenosine was found to mobilize significantly both GM-CFC and granulocytes after both single and repeated administration of DP + AMP. These results show that the elevation of extracellular adenosine presents a potent mechanism for mobilization of GM-CFC and granulocytes into the blood. When the combination of DP + AMP + G-CSF was given under the 4-d regimen, the mobilizing effects of its administration were additive when compared with those of DP + AMP alone or G-CSF alone. The observed ability of the drugs elevating extracellular adenosine to enhance the mobilizing action of G-CSF points out possible practical utilization of the findings presented here. This conclusion is further supported by the results of an additional experiment which indicate that blocking of haemodynamic side effects of drugs elevating extracellular adenosine by noradrenaline does not suppress their mobilizing effects.

• MeSH
• adenosin metabolismus   MeSH
• adenosinmonofosfát farmakologie   MeSH
• dipyridamol farmakologie   MeSH
• extracelulární prostor metabolismus   MeSH
• faktor stimulující kolonie granulocytů farmakologie   MeSH
• granulocyty cytologie   MeSH
• hematopoetické kmenové buňky cytologie   MeSH
• makrofágy cytologie   MeSH
• myši inbrední C57BL MeSH
• myši inbrední CBA MeSH
• myši MeSH
• počet buněk MeSH
• pohyb buněk MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosin MeSH
• adenosinmonofosfát MeSH
• dipyridamol MeSH
• faktor stimulující kolonie granulocytů MeSH

The aim of this study was to focus on the relationship among the associated genotypes of G (8002) A and -3A/-4A endothelin-1 (ET-1) gene polymorphisms and some clinical and/or biochemical parameters in Czech (Caucasian) patients with chronic heart failure. Included in the study were 103 patients with chronic heart failure (functional classes NYHA II-IV, ejection fraction < 40%). The ET-1 gene polymorphisms were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. A significant decrease in the ET-1-associated genotype AG3A4A number (double heterozygote) was observed in CHF patients with plasma big endothelin levels above 0.7 pmol/L compared to those with levels below 0.7 pmol/L (OR = 0.19; 95% confidence interval = 0.06-0.57; P = 0.005; Pcorr = 0.03). We found a significant decrease in the AG3A4A genotype number in the other groups compared to the group of patients with both big endothelin and endothelin-1 levels under 0.7 pmol/L (OR = 0.22; 95% confidence interval = 0.07-0.79; P = 0.02). The double heterozygote variants of two ET-1 gene polymorphisms were associated with significantly less risk for chronic heart failure with higher levels of big endothelin.

• MeSH
• dospělí MeSH
• endotelin-1 genetika   metabolismus   MeSH
• endoteliny krev   MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• nízký srdeční výdej metabolismus   MeSH
• polymorfismus genetický * MeSH
• proteinové prekurzory krev   genetika   metabolismus   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endotelin-1 MeSH
• endoteliny MeSH
• proteinové prekurzory MeSH

BACKGROUND: Asthma is a common multifactorial disease, the aetiology of which is attributable to both environmental and genetic factors. The endothelial nitric oxide synthase (NOS3) gene has been implicated in asthma pathogenesis. OBJECTIVE: This study investigated associations of 27 base-pair tandem repeat polymorphism in intron 4 and the Glu298Asp (G894T) variant of the NOS3 gene with atopic asthma in a Czech population. METHODS: Polymerase chain reaction was used to determine the NOS3 genotypes in subjects with atopic asthma (n = 163) and random controls (n = 209). RESULTS: The NOS3 allele or genotype distributions did not differ significantly between the control and asthma groups. However, the common genotype (bb) of the NOS3 polymorphism in intron 4 was found to be significantly associated with total IgE levels (P = 0.006), specific IgE levels for feathers (P = 0.0002) and a positive skin prick test for hay (P = 0.004). In one atopic patient, we identified an additional 27-bp repeat in the NOS3 gene (NOS3c), which occurred in heterozygous combination with the NOS3b allele (NOS3b/c genotype). In addition, we describe a new polymorphism (A5495G) in the NOS3 gene, which was in almost complete linkage disequilibrium with the NOS3 repeat polymorphism in intron 4. The Glu298Asp variant was not associated with asthma and/or related atopic phenotypes in our study. CONCLUSION: Neither the NOS3 'b' allele nor the NOS3 'b/b' genotype showed any general association with atopic asthma, but they were associated with atopy-related phenotypes. We conclude that the NOS3 gene polymorphisms may act as disease modifiers in atopic asthma phenotype in our population.

• MeSH
• bodová mutace * MeSH
• bronchiální astma enzymologie   genetika   imunologie   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• imunoglobulin E krev   MeSH
• kožní testy MeSH
• lidé MeSH
• mladiství MeSH
• neparametrická statistika MeSH
• polymerázová řetězová reakce MeSH
• rozdělení chí kvadrát MeSH
• sekvenční analýza DNA MeSH
• studie případů a kontrol MeSH
• synthasa oxidu dusnatého, typ III MeSH
• synthasa oxidu dusnatého genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• imunoglobulin E MeSH
• NOS3 protein, human MeSH Prohlížeč
• synthasa oxidu dusnatého, typ III MeSH
• synthasa oxidu dusnatého MeSH

Aims of the study were: (i) to determine the prevalence of mutations C282Y and H63D in the HFE gene causing hereditary hemochromatosis in patients with type 2 diabetes mellitus and non-diabetics, (ii) to investigate the relationship among HFE genotypes, serum ferritin and glucose intolerance and (iii) to assess possible association of HFE mutations with the susceptibility to develop late diabetic complications in the Czech population. Two approaches were employed - the case-control study comprising diabetics and non-diabetic controls (n = 326) and the cross-sectional study comprising subjects with a previously unknown defect of glucose tolerance (n = 113, oral glucose tolerance test performed in each subject). Allele frequencies of C282Y and H63D did not differ between diabetic and control groups nor among subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes. Ferritin levels significantly differed between diabetic and non-diabetic women (P<1.10 (-3)) and among subjects with NGT, IGT and diabetes (P<0.05). Differences in ferritin levels related to particular genotypes of C282Y and H63D were not detected. Prevalence of diabetes in the first and second quartiles of ferritin distribution differed highly significantly from the prevalence in the third and fourth quartiles in women (P = 0.000037), OR = 3.50 (95% CI, 1.89-6.48). The extent of diabetic late complications did not correlate with ferritin plasma levels.

• MeSH
• běloši MeSH
• diabetes mellitus 2. typu krev   genetika   MeSH
• dospělí MeSH
• ferritin krev   MeSH
• genotyp MeSH
• hemochromatóza genetika   MeSH
• histokompatibilita - antigeny třídy I genetika   MeSH
• homozygot MeSH
• inzulin krev   MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• pohlavní dimorfismus MeSH
• polymorfismus genetický * MeSH
• protein hemochromatózy MeSH
• průřezové studie MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• substituce aminokyselin MeSH
• tělesná konstituce 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
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• ferritin MeSH
• HFE protein, human MeSH Prohlížeč
• histokompatibilita - antigeny třídy I MeSH
• inzulin MeSH
• krevní glukóza MeSH
• membránové proteiny MeSH
• protein hemochromatózy MeSH

BACKGROUND: The study was designed to investigate the associations among polymorphisms TNF-B Ncol and TNF-alpha -308G/A, plasma TNF-alpha levels and metabolic and anthropometric parameters related to insulin sensitivity in a set of 113 Caucasian subjects undergoing oral glucose tolerance test (oGTT). METHODS: Genotypes were detected by PCR; BMI, WHR, glycemia during oGTT, fasting immunoreactive insulin, fasting C-peptide, HbA(1c), total cholesterol, triglycerides, HDL, LDL and plasma TNF-alpha levels were measured in each subject. RESULTS: Type 2 diabetes was diagnosed in 10 subjects, impaired glucose tolerance (IGT) in 41, normal glucose tolerance (NGT) in 62. Significant differences among genotypes of the TNF-B Ncol were observed for FPG (P=0.0063), LDL (P=0.0179) and marginally for total cholesterol (P=0.0763) in NGT group. After the classification of NGT subjects into obese and non-obese according to BMI, associations of TNF-B Ncol with FPG, LDL and cholesterol were proved in non-obese subgroup only. TNF-alpha -308G/A polymorphism was not associated with any of the parameters studied. TNF-alpha levels did not revealed difference among NGT, IGT and DM groups or genotype-dependent differences. CONCLUSIONS: Our results indicate significant association of the TNF-B Ncol polymorphism with FPG, LDL and total cholesterol in normoglycemic non-obese Caucasian subjects. This polymorphism could be involved in genetic modulation of glucose and lipid homeostasis and regulation of insulin sensitivity already in healthy state. Disturbances of this regulation could be component of pathogenesis of type 2 diabetes mellitus.

• MeSH
• analýza rozptylu MeSH
• běloši genetika   MeSH
• diabetes mellitus 2. typu genetika   MeSH
• dospělí MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• lymfotoxin-alfa genetika   MeSH
• omezení příjmu potravy MeSH
• polymorfismus genetický * MeSH
• porucha glukózové tolerance genetika   MeSH
• referenční hodnoty MeSH
• restrikční endonukleasy typu II * MeSH
• senioři MeSH
• tělesná konstituce 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
• Geografické názvy
• Evropa MeSH
• Názvy látek
• endodeoxyribonuclease NcoI MeSH Prohlížeč
• krevní glukóza MeSH
• lipidy MeSH
• lymfotoxin-alfa MeSH
• restrikční endonukleasy typu II * MeSH