title: [Genetic predisposition to dyslipidemia].
abstract: Lipid metabolism is regulated by several factors, such as apolipoproteins, lipoprotein receptors, enzymes, and transfer proteins. From the early 1980s until now, molecular biology has been developing rapidly. Hence, genetic analyses have accelerated all over the world. Using these techniques, many genetic investigations have been performed in large-scale studies, which revealed the close associations between genetic abnormalities of the above-mentioned factors and a variety of dyslipidemic disorders. In recent years, novel genes which regulate cholesterol metabolism were reported. For instance, proprotein convertase subtilisin kexin type 9 (PCSK9) and autosomal recessive hypercholesterolemia (ARH) were found as causal genes in patients whose phenotypes are similar to familial hypercholesterolemia. Niemann-Pick C1-Like 1 (NPC1L1), ATP-binding cassette (ABC) A1 (ABCA1), and G5/G8 (ABCG5/G8) were also identified as cholesterol transporters in intestinal epithelial cells and hepatocytes. NPC1L1 is recognized as a target of ezetimibe, a cholesterol absorption inhibitor classified into a new class of lipid-lowering agents. However, we have not been fully successful in identifying candidate genes for all dyslipidemias. In this review, we summarize major dyslipidemic disorders and their causal genes, pathosis, clinical features, diagnosis, and therapeutic approaches. Because it is difficult to analyze genetic abnormalities in clinical laboratories at present, simple and convenient procedures for genetic analyses are expected to be developed in the near future. Such techniques may reveal unknown pathologics for heritable dyslipidemias, which may lead to the search for potential drug targets.
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. sthiraya@juntendo.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D050171:Dyslipidemias / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases