End-stage renal disease (ESRD) is a serious health problem worldwide. The high prevalence of cardiovascular diseases and chronic inflammation remains a major cause of morbidity and mortality in haemodialysed patients. Beside some external factors, genetic predisposition both to renal failure and poor prognosis has been assumed. We have collected a total of 1,014 haemodialysed patients and 2,559 unrelated healthy Caucasians. Single-nucleotide polymorphisms (SNPs) in genes for preproghrelin (GHRL), lipopolysaccharide-binding protein (LBP), HFE and MTHFR were genotyped. In the group of patients, significantly more carriers presented the MTHFR T667T (P = 0.002) and HFE Asp63Asp (P = 0.001) and Cys282Cys (P = 0.01) genotypes. The frequencies of individual SNPs within GHRL and LBP genes did not differ between the patients and controls. The trends in genotype frequencies did not differ between the subgroups of patients with different time on haemodialysis. Common variants in MTHFR and HFE could be a risk factor for all-cause ESRD development, but are not predictors for the survival on haemodialysis.

• MeSH
• chronické selhání ledvin genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• ghrelin genetika   MeSH
• histokompatibilita - antigeny třídy I genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny genetika   MeSH
• membránové proteiny genetika   MeSH
• methylentetrahydrofolátreduktasa (NADPH2) genetika   MeSH
• proteiny akutní fáze genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transportní proteiny genetika   MeSH
• Check Tag
• 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

The dysbalance in the expression of proinflammatory and anti-inflammatory cytokines, which is partially genetically determined, might have essential impact on the clinical outcome and survival of haemodialysed (HD) patients. A total of 500 HD patients and 500 healthy controls were genotyped for three single-nucleotide polymorphisms (SNPs: TNFA -308G/A, IL10 -1082G/A, IFNG +874A/T). To detect the SNPs’ impact on clinical outcome and survival, the HD population was divided into two subgroups depending on the length of HD therapy. The genotypes and phenotypes were correlated with two years followed up laboratory parameters and survival of HD patients. The one-year HD departed patients exhibited significantly higher age (P = 0.0167), C-reactive protein (P = 0.0012), lower nutritional (body mass index, P = 0.0168; dry weight, P = 0.0207; albumin, P = 0.005; triglycerides, P = 0.0174), haematological (red blood cells count, P = 0.0210; haemoglobin, P = 0.0159; haematocrit, P = 0.0368) and HD efficacy parameters (Kt/V, P = 0.0273) compared to long-term HD survivors. Both HD and control population showed similar genotype distribution except for higher occurrence of TNFA A/A homozygotes in healthy controls (P = 0.008). There were no differences in both genotypes and phenotypes in HD subgroups because of the low number of patients in one- -year HD departed patients. Neither genotype nor phenotype had an impact on patients’ survival. From our results we cannot infer that the promoter region SNPs of immune system response-regulating cytokines IL-10, TNF-? and IFN-? have a major impact on clinical outcome of patients on maintenance haemodialysis.

• MeSH
• C-reaktivní protein analýza   metabolismus   MeSH
• chronické selhání ledvin epidemiologie   genetika   terapie   MeSH
• dialýza ledvin MeSH
• financování organizované MeSH
• genotyp MeSH
• hodnocení stavu výživy MeSH
• interferon gama genetika   MeSH
• interleukin-10 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• TNF-alfa genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

Heritability studies have estimated the genetically attributable part of body mass index variance to be in the range of 30-70 %. Rs7566650 (G>C) single-nucleotide polymorphism (SNP) near the promoter of the INSIG2 gene has been identified as associated with body mass index. The gene product of INSIG2 is involved in regulation of fatty acid and cholesterol synthesis. In order to replicate this association we have analysed 2,559 unrelated individuals of Slavonic Caucasian origin from the populationbased Czech MONICA 3-year cohort. Body mass index, waist-hip ratio and plasma lipids (total-cholesterol, HDL-cholesterol, triglycerides) were measured at two independent examinations within three years. We could not detect any association between the SNP rs7566605 and body mass index, waist-hip ratio or lipid parameters, both with or without adjusting for age and gender. Neither the body mass index change nor lipid changes were significantly affected by the INSIG2 gene variant. Our results indicated that this INSIG2 polymorphism has no significant effect on body mass index and plasma lipids in the Czech Slavonic population.

• MeSH
• běloši genetika   MeSH
• dospělí MeSH
• financování organizované MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• index tělesné hmotnosti MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• membránové proteiny genetika   MeSH
• obezita genetika   krev   MeSH
• polymorfismus genetický genetika   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH

Although physiological responses to chronic hypoxia, including pulmonary hypertension and right ventricular hypertrophy, have been well described, the molecular mechanisms involved in cardiopulmonary adaptations are still not fully understood. We hypothesize that adaptive responses to chronic hypoxia are the result of altered transcriptional regulations in the right and left ventricles. Here we report results from the gene expression profiling of adaptive responses in a chronically hypoxic heart. Of 11 analyzed candidate genes, the expression of seven and four genes, respectively, was significantly altered in the right ventricle of hypoxic male and female mice. In the transcriptional profile of the left ventricle, we identified a single expression change in hypoxic males (Vegfa gene). To directly test the role of HIF1, we analyzed the expression profile in Hif1a partially deficient mice exposed to moderate hypoxia. Our data showed that Hif1a partial deficiency significantly altered transcriptional profiles of analyzed genes in hypoxic hearts. The expression changes were only detected in two genes in the right ventricle of Hif1a(+/-) males and in one gene in the right ventricle of Hif1a(+/-) females. First, our results suggest that hypoxia mainly affects adaptive expression profiles in the right ventricle and that each ventricle can respond independently. Second, our findings indicate that HIF1a plays an important role in adaptive cardiopulmonary responses and the dysfunction of HIF1 pathways considerably affects transcriptional regulation in the heart. Third, our data reveal significant differences between males and females in cardiac adaptive responses to hypoxia and indicate the necessity of optimizing diagnostic and therapeutic procedures in clinical practice, with respect to sex.

• MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa nedostatek   genetika   metabolismus   MeSH
• fyziologická adaptace MeSH
• genetická transkripce MeSH
• hematokrit MeSH
• hypoxie genetika   metabolismus   patofyziologie   MeSH
• kardiomegalie genetika   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• messenger RNA metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• plicní hypertenze genetika   metabolismus   patofyziologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese MeSH
• sexuální faktory MeSH
• srdce - funkce komor genetika   MeSH
• srdeční komory metabolismus   patofyziologie   MeSH
• stanovení celkové genové exprese metody   MeSH
• tělesná hmotnost MeSH
• vaskulární endoteliální růstový faktor A genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Variants in the FTO (oxoglutarate-dependent nucleic acid demethylase) gene have been associated with the BMI determination in Western European and North American populations. To widen the geographical coverage of the FTO studies, we have analyzed the association between the FTO gene variant rs17817449 (G>C) and obesity in a Slavic Eastern European population. A total of 3,079 males and 3,602 females 45-69 years old were randomly selected from population registers of seven Czech cities. We examined three indices of obesity: BMI (kg/m(2)), waist circumference, and waist-to-hip ratio (WHR). The FTO rs17817449 variant was significantly associated with BMI both in males (GG 28.7 +/- 4.1; GT 28.3 +/- 3.9; TT 28.0 +/- 3.9; P = 0.003) and females (GG 28.7 +/- 5.2; GT 28.2 +/- 5.1; TT 27.2 +/- 4.9; P < 0.001); the associations were not affected by adjustment for age, smoking, socioeconomic status, and physical activity. The FTO variant was also associated with waist circumference (difference between GG and TT was 1.1 cm (P = 0.043) in men and 2.4 cm (P < 0.001) in women) but this relationship disappeared after adjustment for BMI. Similarly, BMI explained the weak association of FTO with WHR and C-reactive protein. FTO was not associated with plasma total and high-density lipoprotein cholesterol, triglycerides, blood glucose, and blood pressure. These results confirm that in a Slavic population the FTO variant is strongly associated with BMI but not with other risk factors.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• diabetes mellitus genetika   MeSH
• financování organizované MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita etnologie   genetika   krev   MeSH
• obvod pasu MeSH
• poměr pasu a boků MeSH
• proteiny genetika   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH

• Publikační typ
• abstrakty MeSH

• Publikační typ
• abstrakty MeSH