[CETP deficiency].

Abstract

Four different CETP gene mutations have been reported to be causes of increased levels of HDL cholesterol by us and other investigators; two splice donor site mutations involving intron 14, one missense mutation of D442G in exon 15, and one nonsense mutation of Q309X in exon10. Two splice donor site mutations are G (+1)-to-A transition (Int14A) and T insertion at the +3 position (Int14T), and both mutations result in null phenotype as well as a nonsense mutation. In contrast, D442G mutation is partially defective in CETP activity. Two mutations of Int14A and D442G are common mutations in the general Japanese population with a high frequency of the heterozygotes of 2% and 7%, respectively. Heterozygous CETP deficiency is sufficiently common to explain a significant fraction of the variation in HDL-C level in the general Japanese population.