A novel homozygous mutation in CETP gene as a cause of CETP deficiency in a Caucasian kindred.
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).


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.


CONCLUSIONS
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.
Calabresi
Laura
L
Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milano, Italy.
Nilsson
Peter
P
Pinotti
Elisa
E
Gomaraschi
Monica
M
Favari
Elda
E
Adorni
Maria Pia
MP
Bernini
Franco
F
Sirtori
Cesare R
CR
Calandra
Sebastiano
S
Franceschini
Guido
G
Tarugi
Patrizia
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology; D002339:Carotid Arteries; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D008076:Cholesterol, HDL / Q000378:metabolism; D005192:Family Health; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D002784:Cholesterol