Over the last decade, C-reactive protein concentration analyzed by the high sensitivity method (hsCRP) has been proven as a marker of premature atherosclerosis. Concentration exceeding 2 mg/l represents an increased individual risk of myocardial infarction and stroke but strict application of this borderline is complicated by relations of CRP concentrations to other risk factors of cardiovascular diseases. In a large 1 % representative sample of the Czech population, a positive relation of hsCRP to BMI, a waist circumference and triglyceride concentration was documented. Substantial sex differences were found in its relationship to age. Whereas it is continuously increasing in men, this increase appears in women only after menopause. A substantial decrease of body weight and visceral fat volume by increased physical activity is accompanied by significant decrease of hsCRP in young obese women. This decrease was not related to a change of interleukin-6 concentration, although it is supposed to regulate CRP production. CRP concentration is partly under genetic control as a higher concentration in young siblings of probands with proved coronary atherosclerosis was documented. The participation of genes related to lipoprotein metabolism (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP concentrations. We hypothesized that an increased concentration of hsCRP represents a certain marker of proinflammatory status related to central obesity and triglyceride metabolism and it might be related to individual properties of monocytes in atherogenesis., R. Poledne ... [et al.]., and Obsahuje seznam literatury
MicroRNAs (miRNAs) are a class of short non-coding regulatory RNA molecules which play an important role in intracellular communication and cell signaling and which influence cellular processes such as proliferation, differentiation, and cellular death. Over the past two decades, the crucial role of m icroRNAs in controlling tissue homeostasis and disease in cardiovascular systems has become widely recogni zed. By controlling the expression levels of their targets, several miRNAs have been shown to modulate the function of endothelial cells (miR-221/222 and -126), vascular smooth muscle cells (miR-143/145) and macrophages (miR-33, -758, and -26), thereby regulating the development and progression of atherosclerosis. The stability of miRNAs within the blood suggests that circulating miRNAs may function as important biomarkers of disease development and progression. Numerous circulating miRNAs have been found to be dysregulated in a wide variety of different disease states, including diabetes, cancer, and cardiovascular disease., D. Dlouhá, J. A. Hubáček., and Obsahuje bibliografii
The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of ou r study was to confirm the association between NYD-SP18 rs6971091 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the si multaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971091 SNP is related to BMI in males (2000/1 GG 28.3±3.7 kg/m 2 vs. +A 27.5±3.7 kg/m 2 P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971091 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males., J. A. Hubacek, D. Dlouha, V. Lanska, V. Adamkova., and Obsahuje bibliografii
The gene for connexin 37 (Cx37) is considered to be one of the candidate genes for cardiovascul ar disease. We evaluated the association between Cx37 (1019C>T) gene polymorphism (Pro319Ser) and ankle brachial blood pressure index (ABI) in women with type 1 (n=178) and ty pe 2 (n=111) diabetes, and in women from general population (n=862). All women were genotyped for Cx37 polymorphism. In addition to traditional cardiovascular risk factors, ABI was analyzed. In women with type 1 diabetes, ABI significantly decreased from TT to CC carriers (p for trend= 0.008). A similar trend was seen in women with type 2 diabetes (p=0.050) and in women with waist circumference above 75 th percentile (94 cm; n=208) of the general population (p=0.049). The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. The presence of C allele indicated increased risk., J. Piťha, J. A. Hubáček, P. Piťhová., and Obsahuje bibliografii
Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80 ±1.11 vs. 5.76 ±1.06 mmol /l in Czechs; 5.32 ±1.32 vs. 5.71 ±1.08 mmol /l in Lithuanians; 4.88 ±1.05 vs. 5.38±1.13 mmol /l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles., J. A. Hubacek, V. Stanek, M. Gebauerova, V. Adamkova, V. Lesauskaite, D. Zaliaduonyte-Peksiene, A. Tamosiunas, A. Supiyev, A. Kossumov, A. Zhumadilova, J. Pitha., and Obsahuje bibliografii
In the process of population screening for apo E gene polymorphism with the PCR and subsequent restriction analysis, we identified a female who demonstrated heterozygosity for an unusual restriction fragment caused by the loss of a CfoI restriction site. Sequence analysis of the apo E gene was performed and a carrier of the mutant allele with C - T substitution at cDNA position 3817 was identified, which caused an Arg136 - Cys change. The first-line relatives have been screened for this rare mutation with PCR and restriction analysis of PCR products. The complete lipoprotein parameters have been determined in the probands family. In the family, only one child had the same mutant allele as his mother had. The proband (7.49 mmol/l) with her siblings had hypercholesterolemia and a high body mass index (BMI 31.6 kg/m2). By contrast, her son had a normal lipid spectrum with normal BMI. We described the mutation apo E2* (Arg136 - Cys) in a family with elevated lipid levels, but there was no confirmation of the connection between this mutation and type III hyperlipoproteinemia or hyperlipoproteinemia at all. In the case of this mutation, other factors (mainly genetic) are important for the development of lipid metabolism disorders., J. A. Hubáček, J. Piťha, P. Stávek, G. Schmitz, R. Poledne., and Obsahuje bibliografii
Medical genetic research achieved in last decade many efforts leading to better understanding of inherited basis of human diseases. This will not be possible without the participation of patients and controls. However, the general understanding of the background and possibilities of genetic association studies is very low. It was confirmed by study of university of students. Because of the fair of misuses of the individual genetic information, significant part of participants refused the use of already donated blood samples for genetic testing but agreed with using of buccal swabs for the same analysis. To enhance the general knowledge’s of the population, leading to realistic expectations not just about genetic predictive power but also about the eventual risks in behind will be the major mission in the next years., V. Adámková ... [et al.]., and Obsahuje seznam literatury