We assessed association between novel biomarkers of cardiovascular disease and conven tional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER HDL (cholesterol esterifi cation rate in HDL plasma), AIP - Atherogenic Index of Plasma [Log(TG/HDL-C)] as markers of lipoprotein particle size, and CILP2, FTO and MLXIPL polymorphisms, were examined in relation to biomarkers and conventional risk factors. Un ivariate analyses confirmed correlation between AIP, FERHDL and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FERHDL in both genders. In multivariate analysis BMI was the strongest correlate of AIP levels. In multivariate model variability of FER HDL was best explained by AIP (R2 =0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG leve ls explained 43 % of the FER HDL variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FERHDL and AIP related to the known markers of cardiovascular risk provide means to express their subtle interactions by one number. Our novel finding of association between CILP2 polymorphism and FERHDL supports its role in lipid metabolism., K. Rašlová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
a1_In this study we compared several parameters characterizing differences in the lipoprotein profile between members of families with a positive or negative family history of coronary artery disease (CAD). In addition to regular parameters such as the body mass index (BMI), total plasma cholesterol (TC), low density (LDL-C) and high density (HDL-C) cholesterol and triglycerides (TG) we estimated the fractional esterification rate of cholesterol in apoB lipoprotein-depleted plasma (FERHDL) which reflects HDL and LDL particle size distribution. A prevalence of smaller particles for the atherogenic profile of plasma lipoproteins is typical. Log (TG/HDL-C) as a newly established atherogenic index of plasma (AIP) was calculated and correlated with other parameters. The cohort in the study consisted of 29 young (< 54 years old) male survivors of myocardial infarction (MI), their spouses and at least one offspring (MI group; n=116). The control group consisted of 29 apparently healthy men with no family history of premature CAD in three generations, their spouses and at least one offspring (control group; n=124). MI families had significantly higher BMI than the controls, with the exception of spouses. Plasma TC did not significantly differ between MI and the controls. MI spouses had significantly higher TG. Higher LDL-C had MI survivors only, while lower HDL-C had both MI survivors and their spouses compared to the controls. FERHDL was significantly higher in all the MI subgroups (probands 25.85±1.22, spouses 21.55±2.05, their daughters 16.93±1.18 and sons 19.05±1.33 %/h) compared to their respective controls (men 20.80±1.52, spouses 14.70±0.98, daughters 13.23±0.74, sons 15.7±0.76 %/h, p<0.01 to p<0.05). Log (TG/HDL-C) ranged from negative values in control subjects to positive values in MI probands., a2_High correlation between FERHDL and Log (TG/HDL-C) (r = 0.80, p<0.0001) confirmed close interactions among TG, HDL-C and cholesterol esterification rate. The finding of significantly higher values of FERHDL and Log (TG/HDL-C) indicate higher incidence of atherogenic lipoprotein phenotype in members of MI families. The possibility that, in addition to genetic factors, a shared environment likely contributes to the familial aggregation of CAD risk factors is supported by a significant correlation of the FERHDL values within spousal pairs (control pairs: r = 0.51 p<0.01, MI pairs: r = 0.41 p<0.05)., M. Dobiášová, K. Rašlová,H. Rauchová, B. Vohnout, K. Ptáčková, J. Frohlich., and Obsahuje bibliografii
The objective of this study was to evaluate the effect of diet and 677 C®T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene on plasma homocyst(e)ine concentrations in an adolescent population (113 males, age: 14.2±2.4 years; 202 females, age: 14.9±2.1 years) from a region characterized by high cardiovascular mortality. Homocyst(e)ine levels did not differ between males and females (9.4±3.5 and 8.9±3.1 mmol/l, respectively). The homozygosity for the 677 C®T MTHFR mutation was found in 4.6 % of subjects. No differences in homocyst(e)ine levels were found between MTHFR genotypes. Analysis of the diet composition which was performed on a 24-hour daily recall basis and a food frequency questionnaire showed a low daily intake of vitamin B6 (males: 1.13 mg/66 % RDA; females: 0.92 mg/61 % RDA). Daily folic acid intake was 0.21 g/105 % RDA in males and 0.23 g/115 % RDA in females. The results of our study show that the high homocyst(e)ine levels in the adolescent population were not affected by the 677 C®T MTHFR mutation. We conclude that an insufficient dietary intake of vitamin B6 and folic acid is responsible for this finding. This is in accord with the recommendation that the dietary allowances for folate should be reset to the originally prescribed levels of 0.4 g/day which should be sufficient to control the homocysteine levels., K. Rašlová, A. Bederová, J. Gašparovič, P. Blažíček, B. Smolková., and Obsahuje bibliografii
In subjects with Down¢ s syndrome (DS) increased oxidative stress and consequent oxidative cell damage have been reported. The aim of this study was to assess whether the excessive production of free oxygen radicals in these subjects can affect the copper-induced lipid oxidation resistance measured in fresh whole serum. Since a significant elevation of serum uric acid levels, which is an efficient hydrophilic antioxidant, has been repeatedly reported in subjects with DS, we studied the association between increased serum uric acid levels and lipid resistance to oxidation measured directly in serum samples by monitoring the change in absorbance at 234 nm. The group of subjects with Down¢ s syndrome consisted of 25 individuals (aged 18± 5 years). Control group included brothers and sisters of subjects with DS (n = 25, aged 17± 7 years). In subjects with DS, the serum lipid resistance to oxidation (lag time) was significantly higher than in controls (p< 0.05) and a concomitant increase in serum uric acid levels was observed (p< 0.001). A significant positive correlation between lag time and serum uric acid concentration was found in subjects with DS (r = 0.48, p< 0.05), while the positive correlation in the control group was not significant. The results suggest that increased serum uric acid levels repeatedly observed in subjects with DS may be associated with an enhanced resistance of serum lipids to oxidation which is thought to play an important role in the atherogenic process., A. Nagyová, M. Šustrová, K. Rašlová., and Obsahuje bibliografii
Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p .Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Geneti c etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation., D. Gabčová, B. Vohnout, D. Staníková, M. Hučkova, M. Kadurová, M. Debreová, M. Kozárová, Ľ. Fábryová, Slovak FH Study Group, J. Staník, I. Klimeš, K. Rašlová, D. Gašperiková., and Obsahuje bibliografii