title: A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis.
abstract: A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with significantly reduced HDL levels (P = 0.001) and results in a significant decrease in LPL catalytic activity (P < 0.0009). The relative frequency of this mutation increases in those patients with lower HDL cholesterol levels. In vitro mutagenesis and expression studies confirm that this change is associated with a significant reduction in LPL activity. Our data support the relationship between LPL activity and HDL-C levels, and suggest that a specific LPL mutation may be a factor in the development of atherosclerosis.
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Reymer
authors.forename: E
authors.initials: E
authors.lastname: Gagné
authors.forename: B E
authors.initials: BE
authors.lastname: Groenemeyer
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: I
authors.initials: I
authors.lastname: Forsyth
authors.forename: H
authors.initials: H
authors.lastname: Jansen
authors.forename: J C
authors.initials: JC
authors.lastname: Seidell
authors.forename: D
authors.initials: D
authors.lastname: Kromhout
authors.forename: K E
authors.initials: KE
authors.lastname: Lie
authors.forename: J
authors.initials: J
authors.lastname: Kastelein
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D003327:Coronary Disease / Q000209:etiology; D005787:Gene Frequency; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D012307:Risk Factors; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase