Pleiotropy and Heterogeneity in the Expression of Atherogenic Lipoproteins: The IRAS Family Study

Objective: Dyslipidemia is an important determinant of coronary disease. Phenotypic correlations between atherogenic lipids are well established, but the contribution of common genetic influences is less clear. Methods: This study investigates the pair-wise genetic (ρ g ) and environmental (ρ e ) correlations between apoB, LDL-C, HDL-C, and triglyceride (Tg) from Hispanic and African American families of the IRAS Family Study. Results: Heritability estimates (hcirc; 2 ) indicate significant genetic effects on apoB (hcirc; 2 = 0.46 ± 0.05), LDL-C (hcirc; 2 = 0.40 ± 0.05), HDL-C (hcirc; 2 = 0.47 ± 0.05), and Tg (hcirc; 2 = 0.35 ± 0.05) (all p < 0.001). Genetic and environmental correlations were strong for apoB – LDL-C (ρ g = 0.87, ρ e = 0.84), apoB – Tg (ρ g = 0.38, ρ e = 0.65), and HDL-C – Tg (ρ g = –0.42, ρ e = –0.46). Environmental correlations were strong for apoB – HDL-C (ρ e = –0.40), LDL-C – HDL-C (ρ e = –0.24), and Tg – LDL-C (ρ e = 0.33) with weak genetic correlations for these pairs (ρ g = –0.09, 0.10, 0.09 respectively). Conclusions: These results suggest multiple pathways leading to atherogenic dyslipidemia. There are common genetic and environmental influences contributing to variations in apoB and LDL-C as well as apoB and Tg. In addition, the inverse relation between Tg and HDL-C appears to have both genetic and environmental basis. Identifying genes involved in atherogenic dyslipidemia will require careful dissection of the genetic architecture of these pathways.