Abstract | OBJECTIVES: We prospectively investigated the effects of ATP-binding cassette protein-1 (ABCA1) variants on long-term clinical outcome in patients with coronary artery disease (CAD). BACKGROUND: METHODS: We studied cause-specific 10-year mortality and quantitative coronary angiography data from the Regression GRowth Evaluation Statin Study (REGRESS), comprising 884 male CAD patients genotyped for promoter variants encompassing a proximal regulatory region (rs2422493, rs1800976, rs2740483 and rs1800977). Kaplan-Meier, proportional hazards and haplotype analyses were used to ascertain single-variant and multi-marker effects on absolute risk and extent of CAD. RESULTS: Protection from 10-year vascular death could be attributed to the rs2422493 genotype (available in 639 patients) T allele with absolute risk decreasing stepwise from 12.2% to 8.6% to 4.7% per each added allele copy, HR 0.64, p=0.03 and HR 0.53, p=0.04 in the TGCC haplotype context. The TGCC (p=0.04) and TCCT (p=0.003) haplotypes exhibited less extensive CAD. CONCLUSIONS: On a background of contemporary secondary prevention, variation in the ABCA1 promoter influences 10-year risk of vascular death and angiographic extent of CAD in men. These insights contribute to identification of patients sharing a specific prognosis, understanding of its etiological basis and development of strategies of risk reduction in CAD.
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Authors | Jakub J Regieli, Pieter A Doevendans, Diederick E Grobbee, Aeilko H Zwinderman, Yolanda van der Graaf, John J P Kastelein, J Wouter Jukema |
Journal | Atherosclerosis
(Atherosclerosis)
Vol. 218
Issue 2
Pg. 457-63
(Oct 2011)
ISSN: 1879-1484 [Electronic] Ireland |
PMID | 21840005
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- ABCA1 protein, human
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
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Topics |
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
(genetics)
- Aged
- Alleles
- Angiography
(methods)
- Cohort Studies
- Coronary Artery Disease
(genetics, prevention & control)
- Female
- Genetic Variation
- Genotype
- Humans
- Male
- Middle Aged
- Models, Genetic
- Promoter Regions, Genetic
- Prospective Studies
- Regression Analysis
- Risk
- Thrombosis
(genetics)
- Treatment Outcome
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