Specific constellations of lipoprotein particle features, reflected as differences in mean lipoprotein particle diameters, are associated with risk of insulin resistance (IR) and cardiovascular disease (CVD). The associations of lipid profiles with disease risk differ by race/ethnicity, the reason for this is not clear. We aimed to examine whether there were additional genetic differences between racial/ethnic groups on lipoprotein profile. Genotypes were assessed using the Affymetrix 6.0 array in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Association analysis was conducted on fasting mean particle diameters using linear models, adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. Replication of associations reaching P < 1.97 × 10 -05 (the level at which we achieved at least 80 % power to replicate SNP-phenotype associations) was conducted in the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA; N = 2,430). Variants which replicated across both Caucasian populations were subsequently tested for association in the African-American (N = 1,594), Chinese (N = 758), and Hispanic (N = 1,422) populations of MESA. Variants in the APOB gene region were significantly associated with mean VLDL diameter in GOLDN, and in the Caucasian and Hispanic populations of MESA, while variation in the hepatic lipase (LIPC) gene was associated with mean HDL diameter in both Caucasians populations only. Our findings suggest that the genetic underpinnings of mean lipoprotein diameter differ by race/ethnicity. As lipoprotein diameters are modifiable, this may lead new strategies to modify lipoprotein profiles during the reduction of IR that are sensitive to race/ethnicity.
Bibliographical noteFunding Information:
Acknowledgments We are grateful to the staff of the GOLDN study for the assistance in data collection and management. The authors thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. GOLDN is funded by National Heart, Lung, and Blood Institute [grant number U01HL072524-04]. MESA and the MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart, Lung, and Blood Institute. Funding for MESA SHARe genotyping was provided by National Heart, Lung, and Blood Institute [Contract N02-HL-6-4278]. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by National Heart, Lung, and Blood Institute grants and contracts [grant numbers R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259].