Abstract

To understand the role of human cholesteryl ester transfer protein (CETP) in plasma lipoprotein metabolism, CETP activity and mass levels, lipoprotein and apolipoprotein concentrations, and the size of high-density lipoprotein (HDL) were determined in 15 heterozygotes and compared with those of four homozygotes and 20 normolipidemic controls. Plasma CETP activity and mass were totally deficient in the four homozygotes for CETP deficiency, while heterozygotes had approximately half the level of normals. CETP activity positively correlated with CETP mass levels ( r = .95, P < .001). No significant difference was observed in the level of low-density lipoprotein (LDL)-cholesterol among the three groups. The concentration of HDL 2-cholesterol in the heterozygotes was approximately twice as high as that in controls, while that of homozygotes was sixfold higher than that in controls. No significant difference in the HDL 3-cholesterol level was observed among the three groups. The HDL 2-cholesterol to HDL 3-cholesterol ratio of homozygotes was sixfold higher than that of controls, while heterozygotes showed intermediate values between homozygotes and controls. Negative correlations were found between CETP activity and HDL 2-cholesterol level ( r = −.884, P < .001) and between CETP mass and HDL 2-cholesterol level ( r = −.829, P < .001). Plasma apolipoprotein (apo) A-I, C-III, and E were markedly increased in homozygotes, but the differences between normal and heterozygotes were not statistically significant. The HDL size of homozygotes, determined by high-performance liquid chromatography (HPLC), was large, whereas that of heterozygotes was intermediate between homozygotes and normals. These data suggest that CETP may be qualitatively and quantitatively important in determining the plasma concentration, composition, and size of HDL.

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