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.

• MeSH
• ABCA1 protein genetika   MeSH
• adaptorové proteiny vezikulární transportní genetika   MeSH
• apolipoprotein A-I genetika   MeSH
• apolipoprotein A-V genetika   MeSH
• apolipoproteiny E MeSH
• ateroskleróza MeSH
• celogenomová asociační studie MeSH
• dyslipidemie krev   genetika   MeSH
• epigeneze genetická genetika   MeSH
• genetická predispozice k nemoci MeSH
• HDL-cholesterol krev   MeSH
• histonový kód genetika   MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• LDL-cholesterol krev   MeSH
• LDL-receptory genetika   MeSH
• lidé MeSH
• lipidy krev   MeSH
• lipoproteinlipasa genetika   MeSH
• metabolismus lipidů genetika   MeSH
• metylace DNA genetika   MeSH
• N-acetylgalaktosaminyltransferasy genetika   MeSH
• polypeptid-N-acetylgalaktosaminyltransferasa MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   genetika   MeSH
• transportní proteiny pro estery cholesterolu genetika   MeSH
• triglyceridy krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABCA1 protein, human MeSH Prohlížeč
• ABCA1 protein MeSH
• adaptorové proteiny vezikulární transportní MeSH
• APOA1 protein, human MeSH Prohlížeč
• APOA5 protein, human MeSH Prohlížeč
• apolipoprotein A-I MeSH
• apolipoprotein A-V MeSH
• apolipoproteiny E MeSH
• CETP protein, human MeSH Prohlížeč
• HDL-cholesterol MeSH
• intracelulární signální peptidy a proteiny MeSH
• LDL-cholesterol MeSH
• LDL-receptory MeSH
• LDLR protein, human MeSH Prohlížeč
• lipidy MeSH
• lipoproteinlipasa MeSH
• LPL protein, human MeSH Prohlížeč
• N-acetylgalaktosaminyltransferasy MeSH
• protein-serin-threoninkinasy MeSH
• sortilin MeSH Prohlížeč
• transportní proteiny pro estery cholesterolu MeSH
• TRIB1 protein, human MeSH Prohlížeč
• triglyceridy MeSH

AIMS: The effects of cholesteryl ester transfer protein (CETP) inhibition on lipids, inflammation, and markers of high-density lipoprotein (HDL) function, following an acute coronary syndrome (ACS), are unknown. METHODS AND RESULTS: The dal-ACUTE study randomized 300 patients (1 : 1) to dalcetrapib 600 mg/day or placebo within 1 week of an ACS. The primary endpoint was per cent change in HDL-cholesterol (HDL-C) after 4 weeks. Secondary endpoints included apolipoprotein levels, markers of HDL function, and inflammation. Dalcetrapib treatment increased HDL-C and apolipoprotein A1 by 33.7 and 11.8%, respectively (both P < 0.001) and total cholesterol efflux by 9.5% (P = 0.003) after 4 weeks, principally via an increase in non-ATP-binding cassette transporter (ABC) A1-mediated efflux, without statistically significant changes in pre-β1-HDL levels. The increase in total efflux with dalcetrapib correlated most strongly with increases in apolipoprotein A1 and HDL-C (r = 0.46 and 0.43, respectively) rather than the increase in pre-β1-HDL (r = 0.32). Baseline and on-treatment ABCA1-mediated efflux correlated most strongly with pre-β1-HDL levels; in contrast, non-ABCA1-mediated efflux correlated better with apolipoprotein A1 and HDL-C levels. CONCLUSIONS: High-density lipoprotein raised through CETP inhibition with dalcetrapib improves cholesterol efflux, principally via a non-ABCA1-mediated pathway. While HDL-C was increased by one-third, apolipoprotein A1 and total efflux were increased only by one-tenth, supporting the concept of dissociation between improvements in HDL function and HDL-C levels, which may be of relevance to ongoing trials and the development of therapeutic interventions targeting HDL.

• Klíčová slova
• Coronary disease, Lipids, Lipoproteins,
• MeSH
• ABCA1 protein metabolismus   MeSH
• akutní koronární syndrom farmakoterapie   MeSH
• amidy MeSH
• anticholesteremika aplikace a dávkování   MeSH
• apolipoproteiny metabolismus   MeSH
• biologické markery metabolismus   MeSH
• C-reaktivní protein metabolismus   MeSH
• dvojitá slepá metoda MeSH
• estery MeSH
• HDL-cholesterol metabolismus   MeSH
• infarkt myokardu farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• nestabilní angina pectoris farmakoterapie   MeSH
• rozvrh dávkování léků MeSH
• sulfhydrylové sloučeniny aplikace a dávkování   MeSH
• transportní proteiny pro estery cholesterolu antagonisté a inhibitory   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• ABCA1 protein, human MeSH Prohlížeč
• ABCA1 protein MeSH
• amidy MeSH
• anticholesteremika MeSH
• apolipoproteiny MeSH
• biologické markery MeSH
• C-reaktivní protein MeSH
• CETP protein, human MeSH Prohlížeč
• dalcetrapib MeSH Prohlížeč
• estery MeSH
• HDL-cholesterol MeSH
• lipoproteiny MeSH
• sulfhydrylové sloučeniny MeSH
• transportní proteiny pro estery cholesterolu MeSH