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Journal of Lipid Research, Vol. 45, 1008-1026, June 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
Review |
* Lipid Research Center, Laval University Medical Research Center, Laval University, Québec, Canada
Department of Food Science and Nutrition, Laval University, Québec, Canada
Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Québec, Canada
1 To whom correspondence should be addressed. e-mail: marie-claude.vohl{at}crchul.ulaval.ca
Substantial evidence exists suggesting that small, dense LDL particles are associated with an increased risk of coronary heart disease. This disease-related risk factor is recognized to be under both genetic and environmental influences. Several studies have been conducted to elucidate the genetic architecture underlying this trait, and a review of this literature seems timely. The methods and strategies used to determine its genetic component and to identify the genes have greatly changed throughout the years owing to the progress made in genetic epidemiology and the influence of the Human Genome Project. Heritability studies, complex segregation analyses, candidate gene linkage and association studies, genome-wide linkage scans, and animal models are all part of the arsenal to determine the susceptibility genes. The compilation of these studies clearly revealed the complex genetic nature of LDL particles.
This work is an attempt to summarize the growing evidence of genetic control on LDL particle heterogeneity with the aim of providing a concise overview in one read.
Abbreviations: apoB, apolipoprotein B; BMI, body mass index; CAD, coronary artery disease; CETP, cholesteryl ester transfer protein; CHD, coronary heart disease; DGU, density gradient ultracentrifugation; DZ, dizygotic; FATP1, fatty acid transport protein-1; FCHL, familial combined hyperlipidemia; GET, Genetic Epidemiology of Hypertriglyceridemia; GGE, gradient gel electrophoresis; HDL-C, high density lipoprotein cholesterol; LDL-PPD, low density lipoprotein peak particle diameter; LDLR, low density lipoprotein receptor; LDL-Rf, low density lipoprotein flotation rate; LOD, logarithm of the odds; MTP, microsomal triglyceride transfer protein; MZ, monozygotic; QFS, the Québec Family Study; QTL, quantitative trait locus; RFLP, restriction fragment length polymorphism; SOD2, manganese superoxide dismutase; SR-BI, scavenger receptor class B type I
Supplementary key words low density lipoprotein size • heritability • inheritance • linkage study • association study • genome scan
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