Genetic factors affecting HDL levels, structure, metabolism and function.
OBJECTIVE
HDL is a recognized negative risk factor for the cardiovascular diseases. Establishing the genetic determinants of HDL concentration and functions would add to the prediction of cardiovascular risk and point to the biochemical mechanisms underlying this risk. The present review focuses on various approaches to establish genetic determinants of the HDL concentration, structure and function.


RESULTS
While many genes contribute to the HDL concentration and collectively account for half of the variability, polymorphism of individual candidate genes contributes little. There are strong interactions between environmental and genetic influences. Recent findings have confirmed that APOA1 and ABCA1 exert the strongest influence on HDL concentrations and risk of atherosclerosis. CETP and lipases also affect the HDL concentration and functionality, but their connection to the atherosclerosis risk is conditional on the interaction between environmental and genetic factors.


CONCLUSIONS
Analysis of genetic determinants of HDL-cholesterol in patients with specific disease states or in response to the environmental condition may be a more accurate way to assess variations in HDL concentration. This may result in defining the rules of interaction between genetic and environmental factors and lead to understanding the mechanisms responsible for the variations in HDL concentration and functionality.
Sviridov
Dmitri
D
Baker Heart Research Institute, Melbourne, Victoria, Australia. Dmitr.Sviridov@Baker.edu.au
Nestel
Paul J
PJ
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D016632:Apolipoprotein A-I / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D005006:Ethnicity; D005091:Exons; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics; D012307:Risk Factors
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase