title: ABCA1 impacts athero-thrombotic risk and 10-year survival in a contemporary secondary prevention setting.
abstract: OBJECTIVE
  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
  ABCA1 is implicated in the etiology of atherothrombosis and may offer a target to reduce cardiovascular risk. However, the impact of ABCA1 on recurrent cardiovascular disease in a secondary prevention setting is as of yet unknown.
  
  
  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.
authors.affiliation: Department of Cardiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Jakub J
authors.initials: JJ
authors.lastname: Regieli
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000483:Alleles; D000792:Angiography / Q000379:methods; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D012306:Risk; D013927:Thrombosis / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters