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
The long QT syndrome (LQTS) is a monogenic disorder characterized by prolongation of the QT interval on electrocardiogram and syncope or sudden death caused by polymorphic ventricular tachycardia (torsades de pointes). In general, mutations in cardiac ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2) have been identified as a cause for LQTS. About 50-60 % of LQTS patients have an identifiable LQTS causing mutation in one of mentioned genes. In a group of 12 LQTS patients with no identified mutations in these genes we have tested a hypothesis that other candidate genes could be involved in LQTS pathophysiology. SCN1B and KCND3 genes encode ion channel proteins, ANK2 gene encodes cytoskeletal protein interacting with ion channels. To screen coding regions of genes SCN1B, KCND3, and 10 exons of ANK2 following methods were used: PCR, SSCP, and DNA sequencing. Five polymorphisms were found in screened candid ate genes, 2 polymorphisms in KCND3 and 3 in SCN1B. None of found polymorphisms has coding effect nor is located close to splice sites or has any similarity to known splicing enhancer motifs. Polymorphism G246T in SCN1B is a novel one. No mutation directly causing LQTS was found. Molecular mechanism of LQTS genesis in these patients remains unclear., M. Raudenská, A. Bittnerová, T. Novotný, A. Floriánová, K. Chroust, R. Gaillyová, B. Semrád, J. Kadlecová, M. Šišáková, O. Toman, J. Špinar., and Obsahuje bibliografii a bibliografické odkazy
Photosynthetic properties of Cuscuta species, such as chloroplast ultrastructure, contents of chlorophylls, carotenoids, and plastid proteins, photosystem and CO2 fixation activities, and photosynthetic genes composition are reviewed. and N. K. Choudhury, D. Sahu.
Essential hypertension is a major risk factor for several cardiovascular diseases. It is a complex trait resulting from the interactions of multiple genetic and environmental factors. Moreover, not only genetic but also epigenetic inheritance plays a significant role. One can speculate that hypertension develops as a consequence of “errors” in well-coordinated regulatory systems of blood pressure. Errors in the cascade of molecular, biochemical and genetic processes, which regulate blood pressure, have finally enough potential to result in hypertension. Numerous environmental factors surrounding the organism during its development should influence the expression of genetic information. However, despite the considerable research effort, it is still difficult to identify all genes and/or other genetic determinants leading to essential hypertension and other cardiovascular diseases. This is mainly because these diseases usually become a medical problem in adulthood, although their roots might be traced back to earlier stages of ontogeny. The link between distinct developmental periods (e.g. birth and adulthood) should involve changes in gene expression involving epigenetic phenomena. The purpose of the present paper is to bring a piece of light on gene-environmental interactions potentially implicated in the pathogenesis of hypertension., J. Kuneš, J. Zicha., and Obsahuje seznam literatury