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Papers In Press, published online ahead of print July 1, 2006
J. Lipid Res., doi:10.1194/jlr.M600078-JLR200

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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. Kullo^1,*, 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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