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A more recent version of this article appeared on July 1, 2006

Papers In Press, published online ahead of print April 19, 2006
J. Lipid Res., doi:10.1194/jlr.M600078-JLR200
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Submitted on February 14, 2006
Revised on April 13, 2006
Accepted on April 18, 2006

Quantitative trait loci influencing low-density lipoprotein particle size in African Americans

Iftikhar J. Kullo, Keyue Ding, Eric Boerwinkle, Stephen T. Turner, and Mariza de Andrade

Mayo Clinic, Rochester, MN 55905

Corresponding Author: 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=1318, 63.0±9.5 years, 70% women, 78% hypertensive) were ascertained through sibships with = 2 individuals diagnosed with essential hypertension before age 60. LDL particle size was measured by polyacrylamide gel electrophoresis and triglycerides 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 cM, 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 inter-individual variation in LDL particle size and potentially coronary heart disease susceptibility in African Americans.


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