doi: 10.1161/01.RES.0000151332.39871.13
© 2005 American Heart Association, Inc.
Reviews |
Genetics of Variation in HDL Cholesterol in Humans and Mice
From the Jackson Laboratory, Bar Harbor, Me.
Correspondence to Xiaosong Wang, MD, the Jackson Laboratory, 600 Main St, Bar Harbor, ME 04609. E-mail xw{at}jax.org
This Review is part of a thematic series on New Pathways in HDL Metabolism, which includes the following articles:
Antiinflammatory Properties of HDL
Genetics of Variation in HDl Cholesterol in Humans and Mice
New Insights Into the Regulation of HDL Metabolism and Reverse Cholesterol Transport
Endothelial and Antithrombotic Effects of HDL
Daniel Rader Guest Editor
Plasma high-density lipoprotein cholesterol (HDL-C) concentrations are genetically determined to a great extent, and quantitative trait locus (QTL) analysis has been used to identify chromosomal regions containing genes regulating HDL-C levels. We discuss new genes found to participate in HDL metabolism. We also summarize 37 mouse and 30 human QTLs for plasma HDL-C levels, finding that all but three of the mouse QTLs have been confirmed by a second cross or a homologous human QTL, that the mouse QTL map is almost saturated because 92% of recently reported QTLs are repeats of those already found, and that 28 of the 30 human QTLs are located in regions homologous to mouse QTLs. This high degree of concordance between mouse and human QTLs suggests that the underlying genes may be the same. Strategies to more rapidly identify genes underlying mouse and human QTLs for HDL-C include focusing on the mouse and using mouse–human homologies, combining crosses, and haplotyping to narrow the region. Sequence analysis and expression studies can distinguish candidate genes consistent across multiple mouse crosses, and testing the candidate genes in human association studies can provide additional evidence for the candidacy of a gene. Together these strategies can accelerate the pace of finding genes that regulate HDL.
Key Words: high-density lipoprotein • genetics • quantitative trait locus • mouse • human
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