title: [Genetic determination of dyslipidemia - What tell us the results of genome-wide association studies?]
abstract: 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.
authors.forename: Jaroslav Alois
authors.initials: JA
authors.lastname: Hubáček
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D016632:Apolipoprotein A-I / Q000235:genetics; D000072040:Apolipoprotein A-V / Q000235:genetics; D001057:Apolipoproteins E; D050197:Atherosclerosis; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D019175:DNA Methylation / Q000235:genetics; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D042421:Histone Code / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D000097763:Polypeptide N-acetylgalactosaminyltransferase; D000099183:Sortilin
chemical_list: D064286:ATP Binding Cassette Transporter 1; D033942:Adaptor Proteins, Vesicular Transport; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008071:Lipoprotein Lipase; D017350:N-Acetylgalactosaminyltransferases; D017346:Protein Serine-Threonine Kinases; D011973:Receptors, LDL; D014280:Triglycerides; D000097763:Polypeptide N-acetylgalactosaminyltransferase; D000099183:Sortilin; C577836:ABCA1 protein, human; C505693:APOA1 protein, human; C437704:APOA5 protein, human; C506642:CETP protein, human; C573412:LDLR protein, human; C493170:TRIB1 protein, human; C548261:LPL protein, human