A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis

P. W. Reymer; E. Gagné; B. E. Groenemeyer; H. Zhang; I. Forsyth; H. Jansen; J. C. Seidell; D. Kromhout; K. E. Lie; J. Kastelein

doi:https://doi.org/10.1038/ng0595-28

A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis

P. W. Reymer, E. Gagné, B. E. Groenemeyer, H. Zhang, I. Forsyth, H. Jansen, J. C. Seidell, D. Kromhout, K. E. Lie, J. Kastelein

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Research output: Contribution to journal › Article › Academic › peer-review

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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

Original language	English
Pages (from-to)	28-34
Number of pages	7
Journal	Nature Genetics
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/ng0595-28
Publication status	Published - 1995

Keywords

Adult
Aged
Alleles
Animals
Arteriosclerosis
Base Sequence
Cell Line
Cholesterol
Cholesterol, HDL
Coronary Disease
Gene Frequency
Humans
Journal Article
Lipoprotein Lipase
Lipoproteins, LDL
Male
Middle Aged
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Research Support, Non-U.S. Gov't
Risk Factors
Transfection
Triglycerides

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Access to Document

https://doi.org/10.1038/ng0595-28

Cite this

@article{c1f08aebf27e4262b6a4d4b70e6695b6,

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",

keywords = "Adult, Aged, Alleles, Animals, Arteriosclerosis, Base Sequence, Cell Line, Cholesterol, Cholesterol, HDL, Coronary Disease, Gene Frequency, Humans, Journal Article, Lipoprotein Lipase, Lipoproteins, LDL, Male, Middle Aged, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation, Research Support, Non-U.S. Gov't, Risk Factors, Transfection, Triglycerides",

author = "Reymer, {P. W.} and E. Gagn{\'e} and Groenemeyer, {B. E.} and H. Zhang and I. Forsyth and H. Jansen and Seidell, {J. C.} and D. Kromhout and Lie, {K. E.} and J. Kastelein",

year = "1995",

doi = "https://doi.org/10.1038/ng0595-28",

language = "English",

volume = "10",

pages = "28--34",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis

AU - Reymer, P. W.

AU - Gagné, E.

AU - Groenemeyer, B. E.

AU - Zhang, H.

AU - Forsyth, I.

AU - Jansen, H.

AU - Seidell, J. C.

AU - Kromhout, D.

AU - Lie, K. E.

AU - Kastelein, J.

PY - 1995

Y1 - 1995

N2 - 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

AB - 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

KW - Adult

KW - Aged

KW - Alleles

KW - Animals

KW - Arteriosclerosis

KW - Base Sequence

KW - Cell Line

KW - Cholesterol

KW - Cholesterol, HDL

KW - Coronary Disease

KW - Gene Frequency

KW - Humans

KW - Journal Article

KW - Lipoprotein Lipase

KW - Lipoproteins, LDL

KW - Male

KW - Middle Aged

KW - Molecular Sequence Data

KW - Mutagenesis, Site-Directed

KW - Mutation

KW - Research Support, Non-U.S. Gov't

KW - Risk Factors

KW - Transfection

KW - Triglycerides

U2 - https://doi.org/10.1038/ng0595-28

DO - https://doi.org/10.1038/ng0595-28

M3 - Article

C2 - 7647785

SN - 1061-4036

VL - 10

SP - 28

EP - 34

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -