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 (208 mg/dl) and apoA-I (and 272 mg/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 preβ-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.
A novel homozygous mutation in CETP gene as a cause of CETP deficiency in a caucasian kindred / L. CALABRESI, P. NILSSON, E. PINOTTI, M. GOMARASCHI, E. FAVARI, M.P. ADORNI, F. BERNINI, C.R. SIRTORI, S. CALANDRA, G. FRANCESCHINI, P. TARUGI. - In: ATHEROSCLEROSIS SUPPLEMENTS. - ISSN 1567-5688. - 205:2(2009), pp. 506-511.
A novel homozygous mutation in CETP gene as a cause of CETP deficiency in a caucasian kindred
L. CALABRESIPrimo
;M. GOMARASCHI;C.R. SIRTORI;G. FRANCESCHINIPenultimo
;
2009
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 (208 mg/dl) and apoA-I (and 272 mg/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 preβ-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.Pubblicazioni consigliate
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