Abstract 4114: Quantitative Trait Loci Influencing Low-Density Lipoprotein Particle Size in African Americans
Background: Genomic regions that influence LDL particle size in African-Americans are not known. We performed 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.
Methods: 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.
Results: LDL particle size was highly heritable (h2 = 0.78) and significantly (P < 0.0001) genetically correlated with HDL-C (ρG = 0.32) and log triglycerides (ρG = -0.43). Significant evidence of linkage for LDL particle size was present on chromosome 19 (85.3 cM, LOD = 3.07, P = 0.0001; Figure⇓), and suggestive evidence of linkage was present on chromosome 12 (90.8 cM, LOD = 2.02, P = 0.001). 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).
Conclusions: Our study identifies several genomic regions that may contain genes influencing inter-individual variation in LDL particle size and potentially coronary heart disease susceptibility in African Americans.