A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis.
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.
Reymer
P W
PW
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Gagné
E
E
Groenemeyer
B E
BE
Zhang
H
H
Forsyth
I
I
Jansen
H
H
Seidell
J C
JC
Kromhout
D
D
Lie
K E
KE
Kastelein
J
J
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
D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase