👤 Jaroslav A Hubáček

The aim of this study was to analyse the allelic distribution of selected genes in the Czech and Vietnamese populations. We analysed samples from 94 Vietnamese volunteers and 2,859 Czech population-based subjects (2,559 from the Czechs post-MONICA and 300 volunteers from the South region of the Czech Republic). There were significant differences between the two populations for most, but not all, of the SNPs analysed. In particular, the prevalence of risk alleles in the analysed polymorphisms tended to be lower in the Vietnamese community compared to the Czech population, especially within the FTO (rs17817449; associated with obesity risk, P < 0.0001), TCF7L2 (rs7903146; linked to type 2 dia-betes, P < 0.0001) and ADH1B (rs1229984; related to alcohol consumption, P < 0.0001) genes. The genotype within the MCM6/LCT cluster (rs4988235) associated with lactase persistence was not present in the Vietnamese population. Slight genotype differences were detected for one HFE polymorphism (rs1799945 with P = 0.005; but not for rs1800562). Only the genotype frequencies within the MC4R and APOE genes were almost identical in both populations. We conclude that the Vietnamese population may have a lower genetic predisposition to the non-communicable diseases such as obesity or diabetes mellitus. Show less

Dyslipidemia (high levels of plasma triglycerides and total cholesterol/LDL-cholesterol and low HDL-cholesterol) is considered as one of the major factors in the development of atherosclerosis and subsequent myocardial infarction. The final value of lipid parameters results from joint action of genetic predispositions and lifestyle factors (primarily smoking status, physical activity and in lower extent also diet). It is estimated that genetic factors are responsible for 40-80 % of the variability of plasma lipid values. Currently are as predictors DL analyzed mainly single nucleotide polymorphisms (SNPs). A fundamental shift in knowledge of genetic determination DL bring genome-wide association studies (GWAs). These revealed several dozen major polymorphisms in a DNA sequence related to lipid levels. Rather surprisingly, these variants are usually not substitutions of the amino acids, or causing a premature stop codon, but substitutions outside the genes. GWAS also found a number of variants within the genes whose function in lipid metabolism was completely unknown (e.g. gene for sortilin). Polymorphisms in genes for APOE, SORT1, LDLR (affect levels of total cholesterol and LDL-cholesterol), CETP, APOA1, ABCA-1, GALNT-2 (influence HDL-cholesterol) and finally in genes for APOA5, LPL or TRIB1 (affect the levels of triglycerides) but explains max. 30 % of the variability of plasma lipids. It is supposed, that rare polymorphisms/mutations and genetic factors unrelated directly to alterations in the DNA sequence (DNA methylation, histone modifications, regulatory RNA molecules) are responsible for the remaining proportion of DL determination.Key words: gene - cholesterol - interaction - mutation - polymorphism - triglycerides. Show less

We assessed association between novel biomarkers of cardiovascular disease and conventional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER(HDL) (cholesterol esterification 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. Univariate analyses confirmed correlation between AIP, FER(HDL) and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FER(HDL) 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 (R(2) = 0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG levels explained 43 % of the FER(HDL) variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FER(HDL) 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 FER(HDL) supports its role in lipid metabolism. Show less

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. Show less