This Article Full Text Full Text (PDF) All Versions of this Article: 107/18/2361    most recent 01.CIR.0000065577.60129.F5v1 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 Bossé, Y. Articles by Vohl, M.-C. Search for Related Content PubMed PubMed Citation Articles by Bossé, Y. Articles by Vohl, M.-C. Pubmed/NCBI databases UniSTS Related Collections Genetics of cardiovascular disease

(Circulation. 2003;107:2361.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Evidence for a Major Quantitative Trait Locus on Chromosome 17q21 Affecting Low-Density Lipoprotein Peak Particle Diameter

Yohan Bossé, MSc; Louis Pérusse, PhD; Jean-Pierre Després, PhD; Benoît Lamarche, PhD; Yvon C. Chagnon, PhD; Treva Rice, PhD; D.C. Rao, PhD; Claude Bouchard, PhD; Marie-Claude Vohl, PhD

From the Lipid Research Center, CHUL Research Center (Y.B., J.-P.D., B.L., M.-C.V.), the Department of Food Sciences and Nutrition (Y.B., J.-P.D., M.-C.V.), and the Division of Kinesiology, Department of Social and Preventive Medicine (L.P.), Laval University, Ste-Foy, Québec, Canada; the Quebec Heart Institute (J.-P.D.), Institute on Nutraceutical and Functional Food (B.L., M.-C.V.), and Genetic and Molecular Psychiatric Unit (Y.C.C.), Laval University Robert-Giffard Research Center, Beauport, Québec, Canada; the Division of Biostatistics, Washington University School of Medicine, St Louis, Mo (T.R., D.C.R.); and the Pennington Biomedical Research Center, Baton Rouge, La (C.B.).

Correspondence to Marie-Claude Vohl, PhD, Lipid Research Center, CHUL Research Center, TR-93, 2705, Boulevard Laurier, Sainte-Foy, Quebec, G1V 4G2, Canada. E-mail marie-claude.vohl{at}crchul.ulaval.ca

Background— Several lines of evidence suggest that small dense LDL particles are associated with the risk of coronary heart disease. Heritability and segregation studies suggest that LDL particle size is characterized by a large genetic contribution and the presence of a putative major genetic locus. However, association and linkage analyses have thus far been inconclusive in identifying the underlying gene(s).

Methods and Results— An autosomal genome-wide scan for LDL peak particle diameter (LDL-PPD) was performed in the Québec Family Study. A total of 442 markers were genotyped, with an average intermarker distance of 7.2 cM. LDL-PPD was measured by gradient gel electrophoresis in 681 subjects from 236 nuclear families. Linkage was tested by both sib-pair–based and variance components–based linkage methods. The strongest evidence of linkage was found on chromosome 17q21.33 at marker D17S1301, with an LOD score of 6.76 by the variance-components method for the phenotype adjusted for age, body mass index, and triglyceride levels. Similar results were obtained with the sib-pair method (P<0.0001). Other chromosomal regions harboring markers with highly suggestive evidence of linkage (P0.0023; LOD 1.75) include 1p31, 2q33.2, 4p15.2, 5q12.3, and 14q31. Several candidate genes are localized under the peak linkages, including apolipoprotein H on chromosome 17q, the apolipoprotein E receptor 2, and members of the phospholipase A₂ family on chromosome 1p as well as HMG-CoA reductase on chromosome 5q.

Conclusions— This genome-wide scan for LDL-PPD indicates the presence of a major quantitative trait locus located on chromosome 17q and others interesting loci influencing the phenotype.

Key Words: genome • lipoproteins • genetics • genes

This article has been cited by other articles:

				I. J. Kullo, K. Ding, E. Boerwinkle, S. T. Turner, and M. de Andrade Quantitative trait loci influencing low density lipoprotein particle size in African Americans J. Lipid Res., July 1, 2006; 47(7): 1457 - 1462. [Abstract] [Full Text] [PDF]

				K. E. North, H. H. H. Goring, S. A. Cole, V. P. Diego, L. Almasy, S. Laston, T. Cantu, B. V. Howard, E. T. Lee, L. G. Best, et al. Linkage analysis of LDL cholesterol in American Indian populations: the Strong Heart Family Study J. Lipid Res., January 1, 2006; 47(1): 59 - 66. [Abstract] [Full Text] [PDF]

				A. Malhotra, H. Coon, M. F. Feitosa, W.-D. Li, K. E. North, R. A. Price, C. Bouchard, S. C. Hunt, J. K. Wolford, and The American Diabetes Association GENNID Study Gro Meta-analysis of genome-wide linkage studies for quantitative lipid traits in African Americans Hum. Mol. Genet., December 15, 2005; 14(24): 3955 - 3962. [Abstract] [Full Text] [PDF]

				R. M. Krauss Dietary and Genetic Probes of Atherogenic Dyslipidemia Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2265 - 2272. [Abstract] [Full Text] [PDF]

				Y. Yu, D. F. Wyszynski, D. M. Waterworth, S. D. Wilton, P. J. Barter, Y. A. Kesaniemi, R. W. Mahley, R. McPherson, G. Waeber, T. P. Bersot, et al. Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia J. Lipid Res., October 1, 2005; 46(10): 2202 - 2213. [Abstract] [Full Text] [PDF]

				A. M. Shearman, S. Demissie, L. A. Cupples, I. Peter, C. H. Schmid, J. M. Ordovas, M. E. Mendelsohn, and D. E. Housman Tobacco smoking, estrogen receptor {alpha} gene variation and small low density lipoprotein level Hum. Mol. Genet., August 15, 2005; 14(16): 2405 - 2413. [Abstract] [Full Text] [PDF]

				Y. Bosse, Y. C. Chagnon, J.-P. Despres, T. Rice, D. C. Rao, C. Bouchard, L. Perusse, and M.-C. Vohl Compendium of genome-wide scans of lipid-related phenotypes: adding a new genome-wide search of apolipoprotein levels J. Lipid Res., December 1, 2004; 45(12): 2174 - 2184. [Abstract] [Full Text] [PDF]

				M. Tomaszewski, F. J. Charchar, B. Lacka, U. Pesonen, W. Y.S. Wang, E. Zukowska-Szczechowska, W. Grzeszczak, and A. F. Dominiczak Epistatic Interaction Between {beta}2-Adrenergic Receptor and Neuropeptide Y Genes Influences LDL-Cholesterol in Hypertension Hypertension, November 1, 2004; 44(5): 689 - 694. [Abstract] [Full Text] [PDF]

				M. D. Badzioch, R. P. Igo Jr, F. Gagnon, J. D. Brunzell, R. M. Krauss, A. G. Motulsky, E. M. Wijsman, and G. P. Jarvik Low-Density Lipoprotein Particle Size Loci in Familial Combined Hyperlipidemia: Evidence for Multiple Loci From a Genome Scan Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1942 - 1950. [Abstract] [Full Text] [PDF]

				J.-C. Hogue, B. Lamarche, D. Gaudet, M. Lariviere, A. J. Tremblay, J. Bergeron, I. Lemieux, J.-P. Despres, C. Gagne, and P. Couture Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia J. Lipid Res., June 1, 2004; 45(6): 1077 - 1083. [Abstract] [Full Text] [PDF]

				Y. Bosse, L. Perusse, and M.-C. Vohl Genetics of LDL particle heterogeneity: from genetic epidemiology to DNA-based variations J. Lipid Res., June 1, 2004; 45(6): 1008 - 1026. [Abstract] [Full Text] [PDF]

				C.C. Shoulders, E.L. Jones, and R.P. Naoumova Genetics of familial combined hyperlipidemia and risk of coronary heart disease Hum. Mol. Genet., April 1, 2004; 13(90001): R149 - 160. [Abstract] [Full Text] [PDF]

				M. A. Austin, K. L. Edwards, S. A. Monks, K. M. Koprowicz, J. D. Brunzell, A. G. Motulsky, M. C. Mahaney, and J. E. Hixson Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia J. Lipid Res., November 1, 2003; 44(11): 2161 - 2168. [Abstract] [Full Text] [PDF]