CETP deficiency appears to be a frequent cause of increased HDL levels in the population of Japan, possibly because of a founder effect. The results that we observed in heterozygotes suggest that CETP normally plays a part in the regulation of levels of HDL subclass 2. There was no evidence of premature atherosclerosis in the families with CETP deficiency. In fact, the lipoprotein profile of persons with CETP deficiency is potentially antiatherogenic and may be associated with an increased life span.

Plasma high density lipoproteins (HDL) are a negative risk factor for atherosclerosis. Increased HDL is sometimes clustered in families, but a genetic basis has never been clearly documented. The plasma cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from HDL to other lipoproteins and therefore might influence HDL levels. Using monoclonal antibodies, we show that CETP is absent in two Japanese siblings who have markedly increased and enlarged HDL. Furthermore, they are homozygous for a point mutation in the 5'-splice donor site of intron 14 of the gene for CETP, a change that is incompatible with normal splicing of pre-messenger RNA. The results indicate that the family has an inherited deficiency of CETP due to a gene splicing defect, and illustrate the key role that CETP has in human HDL metabolism.

QT dispersion (QTD) on 12-lead ECGs has been proposed as a marker of malignant ventricular tachyarrhythmias, and increased QTD has been reported in long QT syndrome (LQTS). On the other hand, it has been demonstrated that transmural dispersion is associated with ventricular tachyarrhythmias in an experimental model. However, the precise type of QTD or transmural dispersion that contributes most to ventricular tachyarrhythmias in patients with LQTS remains unclear. We evaluated 27 patients with acquired LQTS. These patients were divided into two groups: group A (n =12), patients with polymorphic ventricular tachycardia [torsades de pointes (TdP)], and group B (n =15), patients without TdP. The QT intervals were corrected using Bazett's formula. QTD was measured as the difference between the maximum and the minimum QT intervals, and T wave peak-to-end interval divided by the QT interval (Tpe) in the V5 lead was measured as a new index. Both the corrected QTD (QTDc) and Tpe were significantly larger in group A than in group B. Logistic regression analysis revealed that a reliable predictor for TdP in the QT variables in these patients was not QTDc but Tpe. Cumulative frequency distributions revealed that a Tpe of 0.28 is a good cut-off point for TdP. Tpe did not correlate with the corrected maximum QT interval, whereas the QTDc did correlate with this parameter. In conclusion, Tpe may be the best predictor for TdP in patients with acquired LQTS.