Inherited disorders of HDL metabolism and atherosclerosis

Curr Opin Lipidol. 2005 Apr;16(2):139-45. doi: 10.1097/01.mol.0000162318.47172.ef.

Abstract

Purpose of review: Genetic disorders of HDL metabolism are rare and, as a result, the assessment of atherosclerosis risk in individuals suffering from these disorders has been difficult. Ultrasound imaging of carotid arteries has provided a tool to assess the risk in hereditary hypo and hyperalphalipoproteinemia. This review gives a comprehensive summary.

Recent findings: Epidemiological studies have unequivocally shown that HDL cholesterol levels are inversely related to coronary artery disease risk, but the literature concerning genetic disorders of HDL metabolism provides less convincing information. Fortuitously, we were able to directly compare carotid intima media thickness data of substantial numbers of individuals with mutations in either apolipoprotein A-I (apoA-I), ATP binding cassette AI (ABCA1), lecithin: cholesterol acyltransferase (LCAT) or cholesteryl ester transfer protein. These data show that carriers of an apoA-I mutation exhibit the most pronounced accelerated atherosclerosis compared with those carrying mutations in ABCA1 and LCAT. Heterozygosity for a non-sense mutation in cholesteryl ester transfer protein did, by contrast, not distinguish carriers from controls in terms of intima media thickness progression. We will discuss these results in the context of the current literature.

Summary: Intima media thickness studies have provided evidence that hypoalphalipoproteinemia due to mutations in apoA-I, ABCA1, and LCAT is associated with increased progression of atherosclerosis. In contrast, hyperalphalipoproteinemia as a result of loss of cholesteryl ester transfer protein function is associated with unaltered atherosclerosis progression compared with family controls. This insight is of interest, since it can assist in the prioritizing of antiatherogenic therapy by increasing HDL cholesterol levels.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • Adult
  • Aged
  • Animals
  • Apolipoprotein A-I / genetics
  • Carotid Arteries / diagnostic imaging
  • Carrier Proteins / genetics
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL / blood*
  • Cholesterol, HDL / genetics
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / genetics*
  • Female
  • Glycoproteins / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phosphatidylcholine-Sterol O-Acyltransferase / genetics
  • Tangier Disease / complications
  • Tangier Disease / diagnostic imaging
  • Tangier Disease / genetics*
  • Tunica Intima / pathology
  • Ultrasonography

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoprotein A-I
  • CETP protein, human
  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Glycoproteins
  • Phosphatidylcholine-Sterol O-Acyltransferase