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

Nature Genetics volume 10, pages 28–34 (1995)Cite this article

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.

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Authors and Affiliations

  1. Lipid Research Group, Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Meibergdeef 9, Amsterdam, 1105 AZ, The Netherlands

    Paul W.A. Reymer, Bjorn E. Groenemeyer & Johannes Kastelein

  2. Department of Medical Genetics, University of British Columbia, 416-2125 East Mall, Vancouver, B.C., V6T 1Z4, Canada

    Eric Gagné, Hanfang Zhang, Ian Forsyth & Michael R. Hayden

  3. Departments of Biochemistry and Internal Medicine, Erasmus University of Rotterdam, Dr. van der Molewaterplein 40, Room BD 285, Rotterdam, The Netherlands

    Hans Jansen

  4. Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health & Environmental Protection, Postbox 1, Bilthoven, 3720BA, The Netherlands

    Jaap C. Seidell & Daan Kromhout

  5. Interuniversity Cardiology Institute of the Netherlands, Postbox 19258, Catharijnesingel 52, 3501DG, Utrecht, The Netherlands

    Kong E. Lie

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  1. Paul W.A. Reymer
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Reymer, P., Gagné, E., Groenemeyer, B. et al. A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis. Nat Genet 10, 28–34 (1995). https://doi.org/10.1038/ng0595-28

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