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

Autor: Iftikhar J. Kullo, Keyue Ding, Eric Boerwinkle, Stephen T. Turner, Mariza de Andrade
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Journal of Lipid Research, Vol 47, Iss 7, Pp 1457-1462 (2006)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.M600078-JLR200
Popis: 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 (ρG = 0.32) and log triglycerides (ρG = −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.
Databáze: Directory of Open Access Journals