Genetics
Two novel CETP nonsense mutations produce complete deficiency without coronary disease in a Greek pedigree (J Mol Med 2006)
Original title: 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
Researchers evaluated a Greek family with markedly elevated HDL cholesterol and no history of premature coronary artery disease (CAD), to test whether complete CETP deficiency protects against atherosclerosis, a relationship that had been controversial. The proband, a 45-year-old man with HDL-C of 194 mg/dL and absent CETP activity, was a compound heterozygote for two novel CETP mutations, Q87X and Q165X. A 64-slice multidetector CT scan showed only minimal (less than 10%) narrowing of the proximal left anterior descending artery, with no other evidence of coronary atherosclerosis. Contrary to some previous studies, the authors conclude complete CETP deficiency does not necessarily promote premature atherosclerosis, though it remains unclear whether the lack of coronary disease reflects CETP deficiency itself or the absence of traditional cardiovascular risk factors in this pedigree.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.