CHOLESTERYL ESTER TRANSFER PROTEIN MUTATIONS, PROTEIN-ACTIVITY AND HDL-CHOLESTEROL CONCENTRATION

We have examined a group of North American subjects, selected to inclu de individuals with a wide variety of HDL-cholesterol concentrations f or: 1) mutations in the genes coding for cholesteryl ester transfer pr otein and hepatic lipase, 2) apolipoprotein E genotype, 3) total chole sterol and triglycerides, 4) HDL-triglycerides. Cholesteryl ester tran sfer protein activity was also estimated, using a novel technique that does not require separation of substrate and product. Transfer activi ty was shown to have a monophasic distribution, with a mean activity o f 21 pmol substrate transferred/3 h/mu l plasma. The cholesterol ester transfer activity of the group with HDL-cholesterol >1.60 mmol/l was significantly less than those with HDL-cholesterol <1.60 mmol/l. The c holesteryl ester transfer protein G1533A mutation was detected at an o verall allele frequency of 2.91%. The mutation was more frequent in th e group with HDL-cholesterol <1.60 mmol/l than in those >1.60 mmol/l. It was also more frequent in those with protein activity > 30 pmol/3h/ mu l plasma than in those with activity <30. These data suggest that t his 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 correlati on with the present labour and time intensive assays, this commerciall y available assay offers the potential of rapid, simple analysis of la rge numbers of samples.