Serum lipoprotein lipid concentration and composition in homozygous and heterozygous patients with cholesteryl ester transfer protein deficiency

Six homozygous, 10 heterozygous and 8 unaffected subjects in a CETP deficient family confirmed by CETP gene analysis were studied to characterize serum lipoproteins separated by ultracentrifugation, and to examine the relations between CETP levels and lipoprotein lipid concentration and composition. The serum CETP levels were measured by radioimmunoassay using ¹²⁵I-labeled monoclonal antibodies (TP2). The serum CETP levels in the homozygotes were undetectable and those in the heterozygotes were significantly lower than those in the unaffected subjects (1.5 ± 0.1 vs. 2.2 ± 0.5 μg/ml, P < 0.01). In the HDL fraction, esterified cholesterol (EC) levels in the homozygotes were significantly increased (P < 0.01), and those in the heterozygotes were slightly increased (n.s.), in comparison with those in the unaffected and the normolipidemic controls. The EC levels in the IDL fractions were lower in the homozygotes than in the normolipidemic controls. The EC/triglyceride (TG) molar ratios in IDL, the fraction obtained from the homo- and heterozygotes, were lower than those from the unaffected subjects (P < 0.01 and < 0.01, respectively), and the EC/TG ratios in the HDL fraction obtained from the homo- and heterozygotes were higher than those from the unaffected subjects (P < 0.01 and n.s., respectively). Linear regression analysis showed that positive correlates of the serum CETP levels in all subjects were: IDL-EC (r = 0.463), HDL-TG (r = 0.603) and VLDL- and IDL-EC/TG ratio (r = 0.698 and and 0.843). When the homozygotes were excluded from the analysis, the EC/TG ratios in VLDL IDL were still positively correlated with the serum CETP levels (r = 0.677 and 0.676). Inverse correlates of the serum CETP levels in all subjects were: HDL-EC (r = -0.783) and HDL-EC/TG ratio (r = -0.739). These results suggested that the decreased CETP concentration decreased IDL-cholesterol and increased HDL-cholesterol levels through reducing transport of EC from HDL to IDL, and produced an anti-atherogenic plasma lipoprotein pattern.