Quantitative trait loci influencing low density lipoprotein particle size in African Americans.
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 (h(2) = 0.78) and significantly (P < 0.0001) genetically correlated with HDL-C (rho(G) = 0.32) and log triglycerides (rho(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.
Kullo
Iftikhar J
IJ
Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN 55905, USA. kullo.iftikhar@mayo.edu
Ding
Keyue
K
Boerwinkle
Eric
E
Turner
Stephen T
ST
de Andrade
Mariza
M
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D040641:Quantitative Trait Loci; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides