Journal
JOURNAL OF LIPID RESEARCH
Volume 51, Issue 8, Pages 2032-2057Publisher
ELSEVIER
DOI: 10.1194/jlr.R004739
Keywords
high-density lipoprotein cholesterol; lipoprotein; lipid; genome-wide association studies; coronary artery disease; hypoalphalipoproteinemia; polymorphism; genetic determinant
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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 influencing HDL-C concentrations. Over the past 30 years, candidate gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identified several genetic variations for plasma HDL-C levels. However, the functional role of several of these variants remains unknown, and they do not always correlate with CAD. In this review, we will first 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 findings from the GWA studies and future strategies to elucidate the remaining substantial proportion of HDL-C heritability. Comprehensive 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 identified.-Weissglas-Volkov, D., and P. Pajukanta. Genetic causes of high and low serum HDL-cholesterol. J. Lipid Res. 51: 2032-2057.
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