Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.

• Klíčová slova
• FADS1, FADS2, cluster analysis, fatty acid pattern, haplotypes, metabolic syndrome, single-nucleotide polymorphism,
• Publikační typ
• časopisecké články MeSH

Isolation of genomic DNA is a key step in genetic analysis. The aim of the study was to evaluate the suitability of isolation of DNA from peripheral blood with manual salting-out procedure and automated MagNA system under specific conditions. The impact of storage conditions, type of material (whole blood or blood cells), and method used for DNA extraction were evaluated in terms of DNA yield, its purity, and integrity. Fresh material, and material stored at 2-8°C for 1-4 weeks and frozen at -80°C were tested. For fresh samples, salting-out method gives higher yield than MagNA, irrespectively, on material used. Neither the yield of salting-out method nor its purity decreases during the storage of the samples in the fridge (2-8°C) during 4 weeks. Concerning MagNA, storage of blood cells in the fridge decreases the yield of DNA as well as its purity. For frozen samples, for whole blood, MagNA gives better results while for blood cells, salting-out method seems to be better. For fresh samples, salting-out method is the preferred one, and both whole blood and blood cells can be used. For frozen samples, the preferred method depends on the material.

• Klíčová slova
• Biobank, DNA isolation, MagNA, blood cells, salting out, whole blood,
• MeSH
• chemická frakcionace metody   MeSH
• DNA krev   izolace a purifikace   MeSH
• dospělí MeSH
• konzervace krve MeSH
• lidé středního věku MeSH
• lidé MeSH
• soli chemie   MeSH
• zmrazování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA MeSH
• soli MeSH

States associated with insulin resistance, as overweight/obesity, type 2 diabetes mellitus (DM2), cardiovascular diseases (CVD), some cancers and neuropsychiatric diseases are characterized with a decrease of long-chain polyunsaturated fatty acids (LC-PUFA) levels. Amounts of LC-PUFA depend on the exogenous intake of their precursors [linoleic (LA) and α-linolenic acid (ALA)] and by rate of their metabolism, which is influenced by activities of enzymes, such as Δ6-desaturase (D6D, FADS2), D5D, FADS1, elongases (Elovl2, -5, 6).Altered activities of D5D/D6D were described in plenty of diseases, e.g. neuropsychiatric (depressive disorders, bipolar disorder, dementia), metabolic (obesity, metabolic syndrome, DM2) and cardiovascular diseases (arterial hypertension, coronary heart disease), inflammatory states and allergy (Crohns disease, atopic eczema) or some malignancies. Similar results were obtained in studies dealing with the associations between genotypes/haplotypes of FADS1/FADS2 and above mentioned diseases, or interactions of dietary intake of LA and ALA on one hand and of the polymorphisms of minor allels of FADS1/FADS2, usually characterized by lower activities, on the other hand.The decrease of the desaturases activities leads to decreased concentrations of products with concomitant increased concentrations of substrates. Associations of some SNP FADS with coronary heart disease, concentrations of plasma lipids, oxidative stress, glucose homeostasis, and inflammatory reaction, were described. Experimental studies on animal models and occurrence of rare diseases, associated with missing or with marked fall activities of D5D/D6D emphasized the significance of desaturases for healthy development of organism as well as for pathogenesis of some disease.

• Klíčová slova
• cardiovascular and metabolic diseases., delta-5-desaturase, delta-6-desaturase, genes FADS1/FADS2, inflammation, oxidative stress, polyunsaturated fatty acids,
• MeSH
• delta-5 desaturasa mastných kyselin MeSH
• desaturasy mastných kyselin metabolismus   MeSH
• diabetes mellitus 2. typu enzymologie   genetika   MeSH
• inzulinová rezistence MeSH
• kardiovaskulární nemoci enzymologie   genetika   MeSH
• lidé MeSH
• nádory enzymologie   genetika   MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• zánět enzymologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• delta-5 desaturasa mastných kyselin MeSH
• desaturasy mastných kyselin MeSH
• FADS1 protein, human MeSH Prohlížeč
• nenasycené mastné kyseliny MeSH

INTRODUCTION: We analyzed concentrations of osteopontin (OPN) in patients with pancreatic ductal adenocarcinoma (PDAC) in order to determine firstly whether it is useful to distinguish between PDAC patients and those with chronic non-hereditary pancreatitis (CP) and type 2 diabetes mellitus (T2DM), and secondly whether OPN concentrations depend on the PDAC stage. METHODS: Groups consisting of 64 patients with PDAC, 71 with CP, 67 with T2DM and 48 healthy controls (CON) were enrolled in the study. Controls were compared with regard to levels of OPN, oxidative stress markers, conventional tumor markers and other biochemical parameters. RESULTS: Levels of OPN were higher in patients with PDAC compared with CP patients (P< 0.001), T2DM (P< 0.001) and CON (P< 0.001). There were increased OPN levels in CP patients in comparison with T2DM (P< 0.001) and CON (P< 0.001). Patients with PDAC in stage IV had higher OPN levels than PDAC patients in stage III (P< 0.01). There was no difference in OPN levels of PDAC patients in stage III compared to patients in stage II. CONCLUSION: Our pilot study demonstrates the usefulness of estimating OPN levels to differentiate between pancreatic cancer and chronic pancreatitis. Higher OPN levels over 102 ng/ml could be a potential diagnostic biomarker for pancreatic cancer.

• Klíčová slova
• Osteopontin, chronic non-hereditary pancreatitis, pancreatic ductal adenocarcinoma, type 2 diabetes mellitus,
• MeSH
• biologické markery MeSH
• chronická pankreatitida krev   diagnóza   MeSH
• diabetes mellitus 2. typu krev   diagnóza   MeSH
• diferenciální diagnóza MeSH
• duktální karcinom pankreatu krev   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * MeSH
• nádory slinivky břišní krev   diagnóza   MeSH
• osteopontin krev   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• nádorové biomarkery * MeSH
• osteopontin MeSH

AIM: To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. METHODS: A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. RESULTS: The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). CONCLUSION: Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

• Klíčová slova
• Cirrhosis, Complications of cirrhosis, Hepatic venous pressure gradient, Osteopontin, Portal hypertension, Prognosis, Survival prediction,
• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dospělí MeSH
• jaterní cirhóza krev   diagnóza   mortalita   patofyziologie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• logistické modely MeSH
• odds ratio MeSH
• osteopontin krev   MeSH
• portální hypertenze krev   diagnóza   mortalita   patofyziologie   MeSH
• portální tlak * MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• upregulace 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
• Názvy látek
• biologické markery MeSH
• osteopontin MeSH
• SPP1 protein, human MeSH Prohlížeč

The receptor for advanced glycation end products (RAGE) and its ligands are involved in the pathogenesis of cancer. Glyoxalase I (GLO1) is an enzyme which detoxifies advanced glycation end product (AGE) precursors. The aim of the study was to find out the relationship between four polymorphisms (single nucleotide polymorphism, SNP) of the RAGE gene (AGER) and one SNP of the GLO1 gene and clear cell renal cancer (ccRCC). All polymorphisms (rs1800625 RAGE -429T/C, rs1800624 -374T/A, rs3134940 2184A/G, rs2070600 557G/A (G82S), and GLO1 rs4746 419A/C(E111A)) were determined by PCR-RFLP in 214 patients with ccRCC. A group of 154 healthy subjects was used as control. We found significant differences in the allelic and genotype frequencies of GLO1 E111A (419A/C) SNP between patients and controls-higher frequency of the C allele in ccRCC-58.6 vs. 44.5% in controls, OR (95% CI) 1.77 (1.32-2.38), p = 0.0002 (corrected p = 0.001); OR (95% CI) CC vs. AA 2.76 (1.5-4.80), p = 0.0004 (corrected p = 0.002); and AC+CC vs. AA 2.03 (1.23-3.30), p = 0.0034 (corrected p = 0.017). High aggressiveness of the tumor (grade 4) was associated with the presence of C allele RAGE -429T/C SNP (original p = 0.001, corrected p = 0.005) and G allele RAGE 2184A/G SNP (p < 0.001 and p < 0.005), and for genotypes RAGE -429CC (original p = 0.008, corrected p = 0.04) and RAGE 2184GG SNP (original p = 0.005, corrected p = 0.025). Our results demonstrate the link of E111A GLO1 SNP to the presence of the tumor and the connection of RAGE -429T/C and 2184A/G SNPs with the aggressiveness of the tumor. Further studies are required, especially with respect to potential therapeutic implications.

• MeSH
• alely MeSH
• frekvence genu MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus MeSH
• karcinom z renálních buněk genetika   MeSH
• laktoylglutathionlyasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin genetika   MeSH
• produkty pokročilé glykace genetika   MeSH
• receptor pro konečné produkty pokročilé glykace genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AGER protein, human MeSH Prohlížeč
• GLO1 protein, human MeSH Prohlížeč
• laktoylglutathionlyasa MeSH
• produkty pokročilé glykace MeSH
• receptor pro konečné produkty pokročilé glykace MeSH

OBJECTIVES: PAPP-A is an independent mortality predictor of long term hemodialysis patients and a prognostic marker of acute coronary syndrome in general population. Cys327Cys PAPP-A polymorphism (SNP) (rs12375498) was found to be of significance in preeclampsia and the C allele of the PAPP-A C/G SNP (rs13290387) was defined as an independent risk factor for acute myocardial infarction. The aim of the study was to test the role of these PAPP-A SNPs in long term hemodialysis patients. DESIGN AND METHODS: The studied group consisted of 464 subjects - 319 long term hemodialysis patients (183 men, 136 women, 62±14years) and 145 controls (65 men, 80 women, 49±14years). A subgroup of 211 hemodialysis patients (118 men, 93 women, 63±13years) was prospectively followed up for 4.5years. During the follow up, 111 patients died, 51 of them due to cardiovascular events. PAPP-A SNPs were analyzed by DNA sequencing and serum PAPP-A was measured by TRACE. RESULTS: Both SNPs were in Hardy-Weinberg equilibrium. Allelic and genotype frequencies did not differ between patients and controls and were not related to serum PAPP-A concentrations. Cys327Cys SNP was significant for patients' survival (HR (95% CI): 1.616 (1.110-2.353), nominal p=0.012, corrected p=0.036) while C/G SNP was not. CONCLUSIONS: Our study shows for the first time the significance of Cys327Cys PAPP-A SNP (rs12375498) for overall mortality of long term hemodialysis patients. Although it does not influence the concentration of PAPP-A it still could affect the correct function of this enzyme which has to be clarified in further studies.

• Klíčová slova
• Cardiovascular, Hemodialysis, PAPP-A, Polymorphism, Pregnancy-associated plasma protein A, Renal,
• MeSH
• akutní koronární syndrom genetika   terapie   MeSH
• dialýza ledvin mortalita   MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• polymorfismus genetický genetika   MeSH
• rizikové faktory MeSH
• těhotenský plazmatický protein A genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• těhotenský plazmatický protein A MeSH

OBJECTIVE: Nitric oxide is an important vasoactive mediator. Changes in NO production, caused by functional variants of both endothelial and inducible NO synthase (eNOS, iNOS), might play a role in portal hypertension. The aim was to study the significance of functional eNOS and iNOS gene variants in cirrhotic patients and their interrelationship to both inflammatory and endothelial activation parameters. MATERIAL AND METHODS: One hundred and thirty-two patients with liver cirrhosis (age 36-72 years) and 101 controls were examined for functional variants of eNOS (E298D, 27bpintr4, 786T/C) and iNOS (R221W, S608L) genes. Inflammatory (IL6, IL8, IL10) and vasoactive (sVCAM-1, E-selectin) cytokines were measured using ELISA kits. RESULTS: The frequency of E298D (GG 12%, GT 41%, TT 47%), 28bpintr4 (AA 6%, AB 28%, BB 66%), 786T/C genotypes (CC 17%, CT 45%, TT 38%), as well as R221W (CC 93%, CT 7%, TT 0%), and S608L (CC 65%, CT 32%, TT 3%) genotypes in cirrhotic patients did not differ from the controls (p > 0.05 for all comparisons). No relationship was found between the frequency of these genotypes and the severity of portal hypertension, or either inflammatory or vasoactive cytokines. A positive correlation was found between hepatic venous pressure gradient and cytokine concentration: sVCAM-1, IL6, IL8, IL10. CONCLUSIONS: Examined eNOS and iNOS variants have no relationship to pathogenesis of liver cirrhosis. Severity of portal hypertension was associated with the changes in endothelial activation.

• MeSH
• cytokiny krev   MeSH
• DNA primery chemie   MeSH
• dospělí MeSH
• ELISA MeSH
• genetická variace MeSH
• genotyp MeSH
• jaterní cirhóza komplikace   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymerázová řetězová reakce metody   MeSH
• portální hypertenze etiologie   genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• synthasa oxidu dusnatého, typ II genetika   MeSH
• synthasa oxidu dusnatého, typ III genetika   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
• Názvy látek
• cytokiny MeSH
• DNA primery MeSH
• NOS2 protein, human MeSH Prohlížeč
• NOS3 protein, human MeSH Prohlížeč
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého, typ III MeSH

OBJECTIVES: The aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy. DESIGN AND METHODS: Polymorphisms of RAGE gene (-429 T/C, -374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy. RESULTS: No differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p=0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r=-0.536, p=0.05). CONCLUSIONS: We did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.

• MeSH
• alanintransaminasa krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetické asociační studie MeSH
• intrahepatální cholestáza krev   genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• komplikace těhotenství krev   genetika   MeSH
• laktoylglutathionlyasa genetika   MeSH
• lidé MeSH
• předčasná porodní činnost krev   genetika   MeSH
• preeklampsie krev   genetika   MeSH
• receptor pro konečné produkty pokročilé glykace krev   genetika   MeSH
• růstová retardace plodu krev   genetika   MeSH
• sekvenční analýza DNA MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alanintransaminasa MeSH
• biologické markery MeSH
• laktoylglutathionlyasa MeSH
• receptor pro konečné produkty pokročilé glykace MeSH

Prognosis of patients with pancreas cancer is very poor. The aim of the study was to test the significance of laboratory parameters in the prognosis of patients with pancreas cancer. The studied group included 57 patients (31 men, 26 women, mean age 65 ± 9 years). Blood was collected at the time of diagnosis of pancreas cancer and basic laboratory parameters, including nutritional and inflammatory markers and tumour markers were measured. Patients were followed up until death (median survival 147 days). Ferritin, iron, albumin, prealbumin, cholinesterase, haemoglobin, C-reactive protein, alkaline phosphatase and carcinoembryonic antigen were significant for patients' prognosis in univariate analysis while CA 19-9, bilirubin, liver, pancreas and kidney tests and lipids were not. Multivariate Cox regression demonstrated ferritin, iron and albumin as independent mortality predictors (RR (95%CI), per standard deviation: ferritin 1.497(1.215-2.241), p = 0.002; albumin, 0.716(0.521-0.977), p = 0.035; iron, 0.678(0.504-0.915), p = 0.010). Iron correlated significantly with albumin (r = 0.397, p = 0.002) but neither iron nor albumin correlated with ferritin. Patients who survived 100 days had significantly lower ferritin (median 239 μg/l vs. non-survivors 435 μg/l, p = 0.014), significantly higher albumin but the difference in serum iron was not quite significant. ROC analysis for ferritin revealed AUC for 100 days survival of 0.710, p = 0.007 (and 0.725, p = 0.004 for 200 days survival). AUC for albumin for 100 days survival was not significant (p = 0.073). This study points out ferritin as an independent mortality predictor in patients with pancreas cancer. High serum levels of ferritin at the time of diagnosis of pancreas cancer indicate bad prognosis of the patient.

• MeSH
• ferritin krev   MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory slinivky břišní krev   mortalita   patologie   MeSH
• pilotní projekty MeSH
• prognóza MeSH
• ROC křivka MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ferritin MeSH
• nádorové biomarkery MeSH