Obesity is a serious health problem worldwide and many genes have been implicated in determination of obesity, but our knowledge of the genes responsible for individual differences in weight loss after physical intervention are poor. One of the candidate genes is a gene for angiotensin-converting enzyme (ACE) ant its insertion/deletion (I/D) polymorphism. We have analyzed the association between the ACE gene variant in intervened obese females. Twenty four unrelated healthy obese (BMI > 29.9 kg/m2, with abdominal type of obesity) premenopausal (age between 25 and 45 years) Czech Caucasian sedentary and non-diabetic females, pre-selected according the ACE I/D polymorphism (twelve II and twelve DD homozygotes) were studied in a medical research centre. They underwent 9 weeks intervention program (combination of the lowering of dietary intake to optimal level for the age and 3 times a week physical activity at fitness centre). The participants were supervised to sustain a heart rate of 65 % of maximum. Anthropometrical, biochemical parameters and body composition (Bodystat 1500) were analyzed before and after the intervention. Our study suggest, that in Czech Caucasian females I/D polymorphism within the ACE gene will have no major effect on weight loss. Interestingly, we have detected, that in obese females II genotype was associated with higher increase in basal metabolic rate (202 kcal per day) then in DD homozygotes (p<0.05), thus at least under some circumstances, this genetic variant may have an slight effect on BMI development., P. Suchánek ... [et al.]., and Obsahuje seznam literatury
High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 ( APOA5 ) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 → Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded., J. A. Hubáček ... [et al.]., and Obsahuje seznam literatury
Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (ε2, ε3 and ε4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the ε2, ε3 and ε4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO ε4 carriers have the highest and APO ε2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles ε2 and ε4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO ε3 allele background., J. A. Hubáček, J. Piťha, V. Adámková, Z. Škodová, V. Lánská, R. Poledne., and Obsahuje bibliografii
Some studies have suggested that there could be an association between the duration of sleep in humans and development of the obesity. We have analyzed the group of the probands (n = 3970, 2038 males and 1932 females, aged 18-65 years), with permanent address in the Central or South Bohemia. We ascertained the relationship between the duration of their sleep (obtained per questionnaire) and body mass index, weight, height, the value of systolic and diastolic blood pressure, heart rate, waist and hip circumference, the values of total-, high density- and low density- cholesterol, thyroid hormone and body exercise performed. The optimal values of the body mass index (and optimal body weight) were associated with the duration of sleep 7 hours per night (P < 0.001). This association was found both in males and females and in both districts. Other anthropometrical and biochemical parameters were not associated with the sleep duration., V. Adámková ... [et al.]., and Obsahuje seznam literatury
Statins are the most commonly used drugs in patients with dyslipidemia. Among the patients, a significant inter-individual variability with supposed strong genetic background in statin treatment efficacy has been observed. Genome wide screenings detected variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes that are among the candidates potentially modifying response to statins. Ten variants (SNPs) within these genes (rs599838, rs646776, rs16996148, rs693, rs515135, rs4420638, rs12654264, rs6511720, rs6235, rs11206510) were analyzed in 895 (46 % men, average age 60.3±13.1 years) patients with dyslipidemia treated with equipotent doses of statins (~90 % on simvastatin or atorvastatin, doses 10 or 20 mg) and selected 672 normolipidemic controls (40 % men, average age 46.5 years). Lipid parameters were available prior to the treatment and after 12 weeks of therapy. Statin treatment resulted in a significant decrease of both total cholesterol (7.00±1.53→5.15±1.17 mmol/l, P<0.0001) and triglycerides (2.03±1.01→1.65±1.23 mmol/l, P<0.0005). Rs599838 variant was not detected in first analyzed 284 patients. After adjustment for multiple testing, there was no significant association between individual SNPs and statin treatment efficacy. Only the rs4420638 (APOE/C1/C4 gene cluster) G allele carriers seem to show more profitable change of HDL cholesterol (P=0.007 without and P=0.06 after adjustment). Results demonstrated that, although associated with plasma TC and LDL cholesterol per se, variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes do not modify therapeutic response to statins., M. Vrablík, ... [et al.]., and Obsahuje seznam literaury
Our previous study showed that a diet enriched with 400 g of carp per week improved plasma lipids in subjects after aortocoronary bypass (CABG). The aim of the present study is to determine whether the differe nt carp farming systems have an impact on the effects of carp meat in secondary cardiovascula r prevention. We examined 3 groups of patients after CABG over a 4-week period of spa treatment (108 persons, 73 males, 35 females, age over 60 years). We found no differences in baseline values of blood pressure or plasma lipids. The patients were given a standard spa diet (controls; N=36) or a diet enriched of 400 g of car p meat per week, enriched omega-3 (N=37) or cereal carp (N=35). Plasma lipid parameters were examined at start and after 4 weeks in a routine laboratory setting. Group consuming omega-3 carp showed the largest decline in total cholesterol, LDL ch olesterol, triglycerides and an increase in HDL cholesterol (all p<0.01). We found that carp meat from the two production systems showed significantly different effects on plasma lipids. Further t rials should be performed to clarify the exact causes of the differences., J. Mraz, T. Zajic, P. Kozak, J. Pickova, P. Kacer, V. Adamek, I. Kralova Lesna, V. Lanska, V. Adamkova., and Obsahuje bibliografii
The apolipoprotein A-V (apo A-V) plays an important role in regulation of triglyceride (TG) concentration in serum. To better understand how apo A-V affects triglyceridemia and glucoregulation, the lipoprotein lipase (LPL) activity was determined using intravenous fat tolerance test (IVFTT) and oral glucose tolerance test (oGTT) was performed in carriers of apolipoprotein A-V gene ( APOAV) variants known to be associated with increased triglyceridemia. Twelve carriers of 19W variant, 16 carriers of -1131C variant, 1 combined heterozygote and 16 control subjects homozygous for wild type variants (19S/-1131T) were selected from a population sample and matched with respect to body mass index and age. The APOAV variants carriers had increased TG, very low density lipoprotein-TG, and apo B concentrations (p < 0.05). The LPL activity evaluated as k2 rate constant for clearance of Intralipid® was 14 % lower in APOAV variants carriers. The depression of nonesterified fatty acids (NEFA) concentration after glucose load was delayed in APOAV variants carriers in spite of the same insulinemia and glycemia. Our results suggest that variants of APOAV combined with increased triglyceridemia are associated with lower LPL activity in vivo and with disturbances of regulation of NEFA concentration after glucose load., J. Kovář, V. Adámková., and Obsahuje bibliografii a bibliografické odkazy
Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results., M. Vrablik, L. Zlatohlavek, T. Stulc, V. Adamkova, M. Prusikova, L. Schwarzova, J. A. Hubacek, R. Ceska., 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
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