Genetic determinants of HDL: Monogenic disorders and contributions to variation

Kathy L.E. Klos, Iftikhar J. Kullo

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations


PURPOSE OF REVIEW: This review focuses on recent progress towards the characterization of genetic variations that contribute to interindividual variation in plasma high-density lipoprotein cholesterol levels in the general population. RECENT FINDINGS: Many of the genes that harbor rare mutations leading to extreme high-density lipoprotein cholesterol levels contain common variation that influences plasma high-density lipoprotein cholesterol in several study populations. Candidate gene association studies provide evidence that some of these variations have an effect on high-density lipoprotein cholesterol, dependent on epistatic interactions or environmental context. Both rare and common variations contribute to interindividual high-density lipoprotein cholesterol variation. Recent comparisons of candidate gene sequences between individuals in the tails of the high-density lipoprotein cholesterol distributions (the upper or lower 1-5%) of several study populations indicate that as many as 20% of individuals with low high-density lipoprotein cholesterol harbor a rare mutation in an investigated gene. For example, the ABCA1 gene region harbors rare mutations and common variants that contribute to interindividual high-density lipoprotein cholesterol variation in the general population. SUMMARY: The genetic control of high-density lipoprotein cholesterol level is complex. Maximizing the utility of genetic knowledge for predicting an individual's high-density lipoprotein cholesterol level or response to intervention will require a better understanding of the action of combinations of genetic variants and environmental exposures.

Original languageEnglish (US)
Pages (from-to)344-351
Number of pages8
JournalCurrent opinion in cardiology
Issue number4
StatePublished - Jul 2007


  • ATP-binding cassette transporter A1
  • Apolipoprotein A-I
  • Cholesteryl ester transfer protein
  • HDL-cholesterol
  • Hepatic lipase
  • Lipoprotein lipase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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