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

Nat Genet. 1995 May;10(1):28-34. doi: 10.1038/ng0595-28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Animals
  • Arteriosclerosis / etiology*
  • Arteriosclerosis / genetics
  • Arteriosclerosis / metabolism
  • Base Sequence
  • Cell Line
  • Cholesterol / metabolism
  • Cholesterol, HDL / metabolism*
  • Coronary Disease / etiology
  • Gene Frequency
  • Humans
  • Lipoprotein Lipase / genetics*
  • Lipoprotein Lipase / physiology
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation*
  • Risk Factors
  • Transfection
  • Triglycerides / metabolism


  • Cholesterol, HDL
  • Lipoproteins, LDL
  • Triglycerides
  • Cholesterol
  • Lipoprotein Lipase