Determinants of low HDL levels in familial combined hyperlipidemia.
In familial combined hyperlipidemia (FCHL), affected family members frequently have reduced levels of HDL cholesterol, in addition to elevated levels of total cholesterol and/or triglycerides (TGs). In the present study, we focused on those determinants that are important regulators of HDL cholesterol levels in FCHL, and measured postheparin plasma activities of hepatic lipase (HL), lipoprotein lipase, cholesterol ester transfer protein, and phospholipid transfer protein (PLTP) in 228 subjects from 49 FCHL families. In affected family members (n = 88), the levels of HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and apolipoprotein A-I were lower than in unaffected family members (n = 88) or spouses (n = 52). The main change was the reduction of HDL2 cholesterol by 25.4% in affected family members (P < 0.001 vs. unaffected family members; P = 0.003 vs. spouses). Affected family members had higher HL activity than unaffected family members (P = 0.001) or spouses (P = 0.013). PLTP activity was higher in affected than unaffected family members (P = 0.025). In univariate correlation analysis, a strong negative correlation was observed between HL activity and HDL2 cholesterol (r = -0.339, P < 0.001). Multivariate regression analysis demonstrated that gender, HL activity, TG, and body mass index have independent contributions to HDL2 cholesterol levels. We suggest that in FCHL, TG enrichment of HDL particles and enhanced HL activity lead to the reduction of HDL cholesterol and HDL2 cholesterol.
Soro
Aino
A
Department of Medicine, University of Helsinki, Finland.
Jauhiainen
Matti
M
Ehnholm
Christian
C
Taskinen
Marja-Riitta
MR
D000328:Adult; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood* / Q000378:metabolism; D005260:Female; D005387:Finland; D006023:Glycoproteins; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000201:enzymology / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D008099:Liver / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D008049:Lipase