Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females

The metabolic and genetic determinants of HDL cholesterol (HDL-C) levels an d HDL turnover were studied in 36 normolipidemic female subjects on a whole -food lowfat metabolic diet. Lipid, lipoprotein, and apolipoprotein levels, lipoprotein size, and apolipoprotein turnover parameters were determined, as were genetic variation at one site in the hepatic lipase promoter and si x sites in the apolipoprotein AI/CIII/AIV gene cluster. Menopause had no si gnificant effect on HDLC or turnover. Stepwise multiple regression analysis revealed that HDL-C was most strongly correlated with HDL size, apolipopro tein A-II (apoA-II), and apolipoprotein A-I (apoA-I) levels, which together could account for 90% of the variation in HDLC. HDL size was inversely cor related with triglycerides, body mass index, and hepatic lipase activity, w hich together accounted for 82% of the variation in HDL size. The hepatic l ipase promoter genotype had a strong effect on hepatic lipase activity and could account for 38% of the variation in hepatic lipase activity. The apoA -I transport rate (AI-TR) was the major determinant of apoA-I levels, but A I-TR was not associated with six common genetic polymorphism in the apoAI/C III/AIV gene cluster. A simplified model of HDL metabolism is proposed, in which A-I and apoA-II levels combined with triglycerides, and hepatic lipas e activity could account for 80% of the variation in HDL-C.