The two novel CETP mutations Gln87X and Gln165X in a compound heterozygous state are associated with marked hyperalphalipoproteinemia and absence of significant coronary artery disease.

High levels of high-density lipoprotein cholesterol (HDL-C) occur with cholesteryl ester transfer protein (CETP) deficiency. However, the extent to which CETP deficiency states may be associated with protection against coronary artery disease (CAD) has been controversial. We evaluated a Greek pedigree with high levels of HDL-C and no history of premature CAD. The proband, a 45-year-old male with an HDL-C of 194 mg/dl with absent CETP activity, was heterozygous for two novel CETP mutations (Q87X and Q165X). A 64-slice multidetector CT scan revealed minimal (<10%) narrowing of the proximal left anterior descending artery without any other evidence of coronary atherosclerosis. In contrast to previous studies, these data suggest that complete CETP deficiency does not promote premature atherosclerosis. However, it remains unclear as to whether the relative lack of coronary atherosclerosis was the direct consequence of CETP deficiency and/or the lack of traditional CAD risk factors.