No abstract

Objective-Loss-of-function mutations of the ATP-binding cassette transporter A1 (ABCA1) gene cause Tangier disease, a rare genetic disorder with accumulation of lipid-laden macrophages and increased risk of atherosclerosis. Common variants of this gene may be a genetic factor for atherosclerosis in the general population. This study was performed to test the reported association between the Ϫ565CϾT polymorphism and atherosclerosis severity and to investigate whether this variant per se had an effect on promoter activity of the ABCA1 gene. Methods and Results-A cohort of patients with coronary atherosclerosis were genotyped for the Ϫ565CϾT polymorphism. Logistic regression analyses showed that homozygotes of the Ϫ565T allele had greatest mean number of diseased coronary arteries, particular in nonsmokers. Real-time reverse-transcriptase polymerase chain reaction showed that in atherosclerotic plaques removed from patients undergoing endarteretomy, ABCA1 expression levels were lowest in those who had the T/T genotype and highest in those of the C/C genotype. Transfection and reporter assays demonstrated that in cultured macrophages, the Ϫ565T allelic promoter had a lower activity in driving gene expression than the Ϫ565C allelic promoter. Electrophoretic mobility shift assays displayed differential binding of nuclear proteins to the 2 alleles. Conclusions-These results indicate that the Ϫ565CϾT polymorphism has an allele-specific effect on ABCA1 gene expression and provide further evidence of a genotypic effect on coronary atherosclerosis severity.

ABSTRACT. This article gives an overview of the role of imaging in the diagnosis and management of acute coronary syndrome.

Publication of surgeon-specific data has coincided with a decrease in both the proportion and variety of cases performed by trainees.