High density lipoproteins, reverse transport of cholesterol, and coronary artery disease. Insights from mutations.

作者：Gerd Assmann, Arnold von Eckardstein, Harald Funke · 发表于：PubMed · 年份：1993 · 被引用次数：91 · 研究领域：Diabetes, Cardiovascular Risks, and Lipoproteins、Cholesterol and Lipid Metabolism、Paraoxonase enzyme and polymorphisms

BACKGROUND: The reverse cholesterol transport model is most widely used to explain both the role of high density lipoproteins (HDL) in lipid metabolism and the inverse association between HDL cholesterol plasma concentration and the risk for coronary artery disease (CAD). As familial HDL cholesterol deficiency is frequently paralleled with a family history of premature CAD, much interest has been directed toward the molecular defects in apolipoproteins and lipid-transfer enzymes involved in the formation and metabolism of HDL. Knowledge of the basic defects in rare HDL-deficiency syndromes and apolipoprotein variants provides genetic markers of whether the presence of these molecular defects accounts for low HDL cholesterol levels and the accompanying coronary risk. METHODS AND RESULTS: Sequence analysis of proteins or DNA from patients with HDL deficiency or hyperalphalipoproteinemia as well as from randomly screened probands has helped to identify a series of molecular defects in the genes of apolipoprotein (apo) A-I, apo A-II, apo A-IV, apo C-III, lecithin cholesterol acyltransferase, and cholesterol ester-transfer protein. Some of these mutations were associated with absent and low levels of HDL cholesterol in homozygous and heterozygous carries, respectively, but only a few homozygotes were at an increased risk of CAD. These mutations were invaluable for gaining insight into structural-functional relations in HDL metabolism. CONCLUSIONS: Mutations in the genes of apo A-I...