Common variants of multiple genes that control reverse cholesterol transport together explain only a minor part of the variation of HDL cholesterol levels

S M Boekholdt, O W Souverein, M W T Tanck, G K Hovingh, J A Kuivenhoven, R I G Peters, H Jansen, P M H Schiffers, E E van der Wall, P A Doevendans, P H Reitsma, A H Zwinderman, J J P Kastelein, J W Jukema

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Abstract

It is assumed that the combined effects of multiple common genetic variants explain a large part of variation of high-density lipoprotein cholesterol (HDL-C) plasma levels, but little evidence exists to corroborate this assumption. It was our objective to study the contribution of multiple common genetic variants of HDL-C-related genes to variation of HDL-C plasma levels. A well-characterized cohort of 546 Caucasian men with documented coronary artery disease was genotyped for common functional variants in genes that control reverse cholesterol transport: ATP-binding cassette transporter A1, apolipoprotein A-I and apolipoprotein-E, cholesteryl ester transfer protein, hepatic lipase, lecithin : cholesterol-acyl transferase, lipoprotein lipase, and scavenger receptor class B type 1. Multivariate linear regression showed that these variants, in conjunction, explain 12.4% (95% confidence interval: 6.9-17.9%) of variation in HDL-C plasma levels. When the covariates smoking and body mass index were taken into account, the explained variation increased to 15.3% (9.4-21.2%), and when 10 two-way interactions were incorporated, this percentage rose to 25.2% (18.9-31.5%). This study supports the hypothesis that multiple, mildly penetrant, but highly prevalent genetic variants explain part of the variation of HDL-C plasma levels, albeit to a very modest extent. Multiple environmental and genetic influences on HDL-C plasma levels still have to be elucidated.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalClinical Genetics
Volume69
Issue number3
DOIs
Publication statusPublished - Mar-2006

Keywords

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Alleles
  • Apolipoprotein A-I
  • Apolipoproteins E
  • Biological Transport, Active
  • Carrier Proteins
  • Cholesterol
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Cohort Studies
  • Coronary Artery Disease
  • Genetic Variation
  • Genotype
  • Glycoproteins
  • Humans
  • Lipase
  • Lipoprotein Lipase
  • Male
  • Middle Aged
  • Models, Biological
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Scavenger Receptors, Class B

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