[Cholesteryl ester transfer protein (CETP) deficiency and increased HDL cholesterol levels...

Four different CETP gene mutations have been identified as 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 exon 10. Two splice donor site mutations are G(+1)-to-A transition (Int14A) and T insertion at +3 position (Int14T), and both mutations result in null phenotype as well as a nonsense mutation. By contrast, the D442G mutation is partially defective in plasma CETP activity. Both Int14A and D442G are common mutations in the general Japanese population with high frequencies of the heterozygotes of 1% and 7%, respectively. Heterozygous CETP deficiency is sufficiently common to explain 5% of the variation in HDL-C level in the general Japanese population, in addition to well-known environmental factors. CETP common mutations may be useful for risk-assessment of coronary heart disease, as a negative and genetic risk factor.