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ABCA1 impacts athero-thrombotic risk and 10-year survival in a contemporary secondary prevention setting

Jakub J Regieli1, Pieter A Doevendans, Diederick E Grobbee

  • 1Department of Cardiology, University Medical Center, Utrecht, The Netherlands.

Atherosclerosis
|August 16, 2011
PubMed

Insights

Genetic variations in the ATP-binding cassette protein-1 (ABCA1) promoter influence cardiovascular disease risk. Specific ABCA1 gene variants are linked to reduced vascular death and less severe coronary artery disease in men.

Area of Science:

  • Cardiovascular Genetics
  • Atherosclerosis Research

Background:

  • ATP-binding cassette protein-1 (ABCA1) plays a role in atherothrombosis.
  • The impact of ABCA1 on recurrent cardiovascular disease (CVD) in secondary prevention is not well understood.

Purpose of the Study:

  • To investigate the association between ATP-binding cassette protein-1 (ABCA1) gene variants and long-term clinical outcomes in patients with coronary artery disease (CAD).

Main Methods:

  • Prospective study of 884 male CAD patients from the Regression GRowth Evaluation Statin Study (REGRESS).
  • Genotyping for ABCA1 promoter variants (rs2422493, rs1800976, rs2740483, rs1800977).
  • Analysis of 10-year cause-specific mortality and quantitative coronary angiography using Kaplan-Meier, proportional hazards, and haplotype analyses.

Main Results:

  • The rs2422493 T allele was associated with a stepwise decrease in 10-year vascular death risk (from 12.2% to 4.7%).
  • Hazard ratios for vascular death were 0.64 (p=0.03) for the genotype and 0.53 (p=0.04) within the TGCC haplotype context.
  • TGCC and TCCT haplotypes were associated with reduced extent of coronary artery disease (CAD).

Conclusions:

  • ABCA1 promoter variations impact 10-year vascular death risk and CAD severity in men undergoing secondary prevention.
  • These findings aid in identifying patients with specific prognoses and developing risk reduction strategies for CAD.
Abstract

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