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We have examined a group of North American subjects, selected to include individuals with a wide variety of HDL-cholesterol concentrations for: 1) mutations in the genes coding for cholesteryl ester transfer protein and hepatic lipase, 2) apolipoprotein E genotype, 3) total cholesterol and triglycerides, 4) HDL-triglycerides. Cholesteryl ester transfer protein activity was also estimated, using a novel technique that does not require separation of substrate and product. Transfer activity was shown to have a monophasic distribution, with a mean activity of 21 pmol substrate transferred/3 h/μl plasma. The cholesterol ester transfer activity of the group with HDL-cholesterol &gt;1.60 mmol/l was significantly less than those with HDL-cholesterol &lt;1.60 mmol/l. The cholesteryl ester transfer protein G1533A mutation was detected at an overall allele frequency of 2.91 %. The mutation was more frequent in the group with HDL-cholesterol &lt;1.60 mmol/l than in those &gt;1.60 mmol/l. It was also more frequent in those with protein activity &gt; 30 pmol/3h/μl plasma than in those with activity &lt;30. These data suggest that this mutation in cholesteryl ester transfer protein is associated with increased transfer activity and reduced HDL-cholesterol concentrations. The cholesteryl ester transfer protein activity assay described here is simple and convenient. Subject to further evaluation and correlation with the present labour and time intensive assays, this commercially available assay offers the potential of rapid, simple analysis of large numbers of samples.

Cholesteryl Ester Transfer Protein Mutations, Protein Activity and HDL-Cholesterol Concentration