Abstract 1452: ABCA1 Promotor Variant -477 C/T Is Related To 10-year Vascular Mortality: The First Step Of Possible Reverse Cholesterol Transport Revisited
INTRODUCTION The ATP binding cassette protein-1 (ABCA1) transporter promotes cholesterol efflux from macrophages constituting the first step of reverse cholesterol transport. Induction of ABCA1 activity potentially offers a new pharmacological target to prevent progression of atherosclerosis and reduce vascular risk. Variation in the ABCA1 gene such as the −477C/T variant has been previously associated with angiographical severity of coronary artery disease (CAD). However, the impact on cardiovascular risk in patients remains unknown. We set out to investigate the impact of ABCA1 C-477T on ten-year outcomes.
METHODS Long term mortality of the REGRESS cohort, comprising 884 male CAD patients, was derived from nation-wide registries. Patients were genotyped for ABCA1 C-477T. Endpoints were defined from recorded ICD codes. Risks according to genotype were estimated using proportional hazard analyses.
RESULTS Death related to ischemic heart diseases (IHD) and vascular diseases occurred in 58 (6.6%) and 71 (8.0%) patients respectively. Genotypes (72% available), comprised 177 (28 %) CC, 351 ( 55 %) CT and 110 (17 %) TT subjects. Hazard ratios (HR) were were 0.71 (0.45–1.14), p=0.16 for IHD- and 0.64 (0.42– 0.97), p=0.03 for vascular disease related death respectively, per each added copy (co-dominant) of the T allele.
DISCUSSION The C-allele of the ABCA1 promoter polymorphism C-477T confers an increased 10-year mortality of atherosclerotic diseases in patients with documented CAD. Since this gene-variant likely influences cellular cholesterol efflux, these results emphasize the relevance of ABCA1 transporter function as a potential target to modify vascular risk.