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.
Hokanson
John E
JE
Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colo. 80262, USA. john.hokanson@uchsc.edu
Langefeld
Carl D
CD
Mitchell
Braxton D
BD
Lange
Leslie A
LA
Goff
David C
DC
Haffner
Steven M
SM
Saad
Mohammad F
MF
Rotter
Jerome I
JI
D000328:Adult; D001741:Black or African American / Q000235:genetics; D001055:Apolipoproteins B / Q000235:genetics*; D008076:Cholesterol, HDL / Q000235:genetics*; D008078:Cholesterol, LDL / Q000235:genetics*; D004198:Disease Susceptibility; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D014280:Triglycerides / Q000235:genetics*
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides