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 (rhog) and environmental (rhoe) correlations between apoB, LDL-C, HDL-C, and triglyceride (Tg) from Hispanic and African American families of the IRAS Family Study.

Results: Heritability estimates (ĥ2) indicate significant genetic effects on apoB (ĥ2=0.46+/-0.05), LDL-C (ĥ2=0.40+/-0.05), HDL-C (ĥ2=0.47+/-0.05), and Tg (ĥ2=0.35+/-0.05) (all p<0.001). Genetic and environmental correlations were strong for apoB-LDL-C (rhog=0.87, rhoe=0.84), apoB-Tg (rhog=0.38, rhoe=0.65), and HDL-C-Tg (rhog=-0.42, rhoe=-0.46). Environmental correlations were strong for apoB-HDL-C (rhoe=-0.40), LDL-C-HDL-C (rhoe=-0.24), and Tg-LDL-C (rhoe=0.33) with weak genetic correlations for these pairs (rhog=-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.