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

Paul W.A. Reymer, Eric Gagné, Bjorn E. Groenemeyer, Hanfang Zhang, Ian Forsyth, Hans Jansen, Jaap C. Seidell, Daan Kromhout, Kong E. Lie, Johannes Kastelein, Michael R. Hayden

Research output: Contribution to journalArticle

222 Scopus citations

Abstract

A reduction of high density lipoprotein cholesterol (HOC) 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 languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalNature Genetics
Volume10
Issue number1
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Genetics

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    Reymer, P. W. A., Gagné, E., Groenemeyer, B. E., Zhang, H., Forsyth, I., Jansen, H., Seidell, J. C., Kromhout, D., Lie, K. E., Kastelein, J., & Hayden, M. R. (1995). A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis. Nature Genetics, 10(1), 28-34. https://doi.org/10.1038/ng0595-28