Thematic Review Series: Genetics of Human Lipid Diseases Genetic causes of high and low serum HDL-cholesterol
Published 2010 · D. Weissglas-Volkov, P. Pajukanta
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Abstract
Plasma levels of HDL cholesterol (HDL-C) have a strong inherited basis with heritability estimates of 40-60%. The well-established inverse relationship between plasma HDL-C levels and the risk of coronary artery disease (CAD) has led to an extensive search for genetic factors infl uenc- ing HDL-C concentrations. Over the past 30 years, candi- date gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identifi ed sev- eral genetic variations for plasma HDL-C levels. However, the functional role of several of these variants remains un- known, and they do not always correlate with CAD. In this review, we will fi rst summarize what is known about HDL metabolism, monogenic disorders associated with both low and high HDL-C levels, and candidate gene studies. Then we will focus this review on recent genetic fi ndings from the GWA studies and future strategies to elucidate the remain- ing substantial proportion of HDL-C heritability. Com- prehensive investigation of the genetic factors conferring to low and high HDL-C levels using integrative approaches is important to unravel novel pathways and their relations to CAD, so that more effective means of diagnosis, treatment, and prevention will be identifi ed. —Weissglas-Volkov, D., and P. Pajukanta. Genetic causes of high and low serum HDL-cholesterol. J. Lipid Res. 51: 2032-2057.