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Originally published In Press as doi:10.1194/jlr.M600078-JLR200 on April 19, 2006
Papers In Press, published online ahead of print July 1, 2006
J. Lipid Res., doi:10.1194/jlr.M600078-JLR200
Journal of Lipid Research, Vol. 47, 1457-1462, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology
Quantitative trait loci influencing low density lipoprotein particle size in African Americans
Iftikhar J. Kullo1,*,
Keyue Ding*,
Eric Boerwinkle ,
Stephen T. Turner and
Mariza de Andrade**
* Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN 55905
Division of Nephrology and Hypertension, Mayo Clinic and Foundation, Rochester, MN 55905
** Division of Biostatistics, Mayo Clinic and Foundation, Rochester, MN 55905
Human Genetics Center and Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX 77030
Published, JLR Papers in Press, April 19, 2006.
1 To whom correspondence should be addressed. e-mail: kullo.iftikhar{at}mayo.edu
Genomic regions that influence LDL particle size in African Americans are not known. We performed family-based linkage analyses to identify genomic regions that influence LDL particle size and also exert pleiotropic effects on two closely related lipid traits, high density lipoprotein cholesterol (HDL-C) and triglycerides, in African Americans. Subjects (n = 1,318, 63.0 ± 9.5 years, 70% women, 79% hypertensive) were ascertained through sibships with two or more individuals diagnosed with essential hypertension before age 60. LDL particle size was measured by polyacrylamide gel electrophoresis, and triglyceride levels were log-transformed to reduce skewness. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Univariate and bivariate linkage analyses were performed using a variance components approach. LDL particle size was highly heritable (h2 = 0.78) and significantly (P < 0.0001) genetically correlated with HDL-C ( G = 0.32) and log triglycerides ( G = 0.43). Significant evidence of linkage for LDL particle size was present on chromosome 19 [85.3 centimorgan (cM), log of the odds (LOD) = 3.07, P = 0.0001], and suggestive evidence of linkage was present on chromosome 12 (90.8 cM, LOD = 2.02, P = 0.0011). Bivariate linkage analyses revealed tentative evidence for a region with pleiotropic effects on LDL particle size and HDL-C on chromosome 4 (52.9 cM, LOD = 2.06, P = 0.0069). These genomic regions may contain genes that influence interindividual variation in LDL particle size and potentially coronary heart disease susceptibility in African Americans.
Supplementary key words bivariate genetic linkage high density lipoprotein cholesterol triglycerides

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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