In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 21, No. 6 ( 2001-06), p. 985-990
Abstract:
Abstract —Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) from HDL to apolipoprotein (apo) B–containing lipoproteins and plays a crucial role in reverse cholesterol transport, which is a major protective system against atherosclerosis. Genetic CETP deficiency is the most common cause of a marked hyperalphalipoproteinemia (HALP) in the Japanese, and various mutations have been identified in the coding region as well as in the exon/intron boundaries in the CETP gene. In the present study, we identified a novel mutation in the promoter region of the CETP gene. This mutation was a G-to-A substitution at the −69 nucleotide of the promoter region (−69 G→A), corresponding to the second nucleotide of the PEA3/ETS binding site (C G GAA) located upstream of the putative TATA box. Four (2.0%) of 196 unrelated subjects with a marked HALP (HDL cholesterol ≥2.59 mmol/L=100 mg/dL) were revealed to be heterozygous for the −69 G→A mutation, and the allelic frequency of the mutant was 0.0102 in the subjects with a marked HALP. The subjects with the −69 G→A mutation had low plasma CETP levels. Reporter gene assay showed that this mutation markedly reduced the transcriptional activities in HepG2 cells (8% of wild type). These results suggested that this mutation would be dominant negative. In conclusion, a novel −69 G→A mutation in the CETP gene causes the decreased transcriptional activity leading to HALP.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.21.6.985
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
1494427-3