Genetics
A novel CETP R37X mutation causes complete CETP deficiency and extreme HDL elevation without atherosclerosis in a Swedish man (Atherosclerosis 2009)
Original title: A novel homozygous mutation in CETP gene as a cause of CETP deficiency in a Caucasian kindred
A 63-year-old Swedish man with markedly elevated HDL-cholesterol (208 mg/dl) and apoA-I (272 mg/dl) was found homozygous for a novel exon 2 point mutation in the CETP gene (c.109 C>T), creating a premature stop codon (R37X). His plasma CETP mass and activity were undetectable, and his HDL was characterized by a predominance of large particles with enhanced prebeta-HDL content. His sons, heterozygous for the mutation, had reduced plasma CETP activity and moderately elevated HDL-cholesterol. Serum from CETP-deficient family members showed normal or enhanced cholesterol efflux via ABCG1/SR-BI, while ABCA1-mediated efflux and macrophage cholesterol removal were lower than normal. The proband was healthy with no atherosclerotic plaques in the carotid or femoral arteries, leading the authors to conclude that complete CETP deficiency does not predispose to atherosclerosis in the absence of major cardiovascular risk factors.
Original abstract
Objective: To analyze the cholesteryl ester transfer protein (CETP) gene and the plasma HDL phenotype in a Caucasian subject with extremely elevated plasma high density lipoprotein-cholesterol (HDL-C).
Methods And Results: The proband, a 63-year-old male of Swedish ancestry with elevated HDL-C (208mg/dl) and apoA-I (and 272mg/dl), was found to be homozygous for a point mutation in exon 2 of CETP gene (c.109 C>T) resulting in a premature termination codon (R37X). Plasma CETP mass and activity were undetectable. Plasma HDL were characterized by predominance of large HDL with enhanced prebeta-HDL content. The proband's sons, heterozygotes for the mutation, had reduced plasma CETP activity and moderately elevated HDL-C. Serum of CETP deficient subjects showed a normal or enhanced cholesterol efflux capacity via ABCG1/SR-BI; cholesterol efflux via ABCA1 and macrophage cholesterol removal were lower than normal. The proband was healthy and had no atherosclerotic plaques in carotid or femoral arteries.
Conclusion: Complete CETP deficiency caused by mutations in CETP gene is exceedingly rare in Caucasians; the description of this single case indicates that CETP deficiency does not predispose to atherosclerosis in the absence of major cardiovascular risk factors.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.