This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, X. Articles by Paigen, B. Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Paigen, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Related Collections Genetics of cardiovascular disease Lipid and lipoprotein metabolism Animal models of human disease

(Circulation Research. 2005;96:27.)
© 2005 American Heart Association, Inc.

Reviews

Genetics of Variation in HDL Cholesterol in Humans and Mice

Xiaosong Wang, Beverly Paigen

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

This article has been cited by other articles:

				S. Sheehan, S.-W. Tsaih, B. L. King, C. Stanton, G. A. Churchill, B. Paigen, and K. DiPetrillo Genetic analysis of albuminuria in a cross between C57BL/6J and DBA/2J mice Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1649 - F1656. [Abstract] [Full Text] [PDF]

				J. E. Wergedal, C. L. Ackert-Bicknell, W. G. Beamer, S. Mohan, D. J. Baylink, and A. K. Srivastava Mapping genetic loci that regulate lipid levels in a NZB/B1NJxRF/J intercross and a combined intercross involving NZB/B1NJ, RF/J, MRL/MpJ, and SJL/J mouse strains J. Lipid Res., August 1, 2007; 48(8): 1724 - 1734. [Abstract] [Full Text] [PDF]

				D. K. Arnett and for the Writing Group Summary of the American Heart Association's Scientific Statement on the Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1682 - 1686. [Full Text] [PDF]

				M. T. Villarreal-Molina, C. A. Aguilar-Salinas, M. Rodriguez-Cruz, D. Riano, M. Villalobos-Comparan, R. Coral-Vazquez, M. Menjivar, P. Yescas-Gomez, M. Konigsoerg-Fainstein, S. Romero-Hidalgo, et al. The ATP-Binding Cassette Transporter A1 R230C Variant Affects HDL Cholesterol Levels and BMI in the Mexican Population: Association With Obesity and Obesity-Related Comorbidities Diabetes, July 1, 2007; 56(7): 1881 - 1887. [Abstract] [Full Text] [PDF]

				D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]

				I. M. Stylianou, S.-W. Tsaih, K. DiPetrillo, N. Ishimori, R. Li, B. Paigen, and G. Churchill Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F2 Crosses Genetics, October 1, 2006; 174(2): 999 - 1007. [Abstract] [Full Text] [PDF]

				H. Wittenburg, M. A. Lyons, R. Li, U. Kurtz, X. Wang, J. Mossner, G. A. Churchill, M. C. Carey, and B. Paigen QTL mapping for genetic determinants of lipoprotein cholesterol levels in combined crosses of inbred mouse strains, J. Lipid Res., August 1, 2006; 47(8): 1780 - 1790. [Abstract] [Full Text] [PDF]

				A. K. Srivastava, S. Mohan, G. L. Masinde, H. Yu, and D. J. Baylink Identification of quantitative trait loci that regulate obesity and serum lipid levels in MRL/MpJ x SJL/J inbred mice J. Lipid Res., January 1, 2006; 47(1): 123 - 133. [Abstract] [Full Text] [PDF]