ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment.
OBJECTIVE
Our goals were to examine the relationships of a specific ATP-binding cassette transporter A1 (ABCA1) variant, rs2230806 (R219K), on baseline lipids, low-density lipoprotein cholesterol (LDL-C) lowering due to pravastatin, baseline heart disease, and cardiac endpoints on trial.


RESULTS
The ABCA1 R219K variant was assessed in 5414 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and followed for a mean of 3.2 years. Of these subjects 47.6% carried the variant, with 40.0% carrying one allele, and 7.6% carrying both alleles. No effects on baseline LDL-C levels were noted, but mean HDL-C increased modestly according to the number of variant alleles being present (1.27 vs 1.28 vs 1.30 mmol/L, p = 0.024). No relationships between the presence or absence of this variant and statin induced LDL-C lowering response or CHD at baseline were noted. However within trial those with the variant as compared to those without the variant, the overall adjusted hazard ratio for new cardiovascular disease (fatal CHD, non-fatal myocardial infarction, or fatal or non-fatal stroke) was 1.22 (95% CI 1.06-1.40, p = 0.006), while for those in the pravastatin group it was 1.41 (1.15-1.73, p = 0.001), and for those in the placebo group it was 1.08 (0.89-1.30, p = 0.447) (p for interaction 0.058).


CONCLUSIONS
Our data indicate that subjects with the ABCA1 R219K variant may get significantly less heart disease risk reduction from pravastatin treatment than those without the variant.
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA; Department of Cardiology, Kanazawa Medical University, Uchinada, Japan.
Hironobu
H
Akao
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA; Boston Heart Diagnostics, Framingham, MA, USA.
Eliana
E
Polisecki
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA; Boston Heart Diagnostics, Framingham, MA, USA.
Ernst J
EJ
Schaefer
Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Gerontology, and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.
Stella
S
Trompet
Robertson Centre of Biostatistics, University of Glasgow, Glasgow, Scotland, UK.
Michele
M
Robertson
Robertson Centre of Biostatistics, University of Glasgow, Glasgow, Scotland, UK.
Ian
I
Ford
Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Gerontology, and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.
J Wouter
JW
Jukema
Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Gerontology, and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.
Anton J M
AJ
de Craen
Department of Vascular Biochemistry, University of Glasgow, Glasgow, Scotland, UK.
Christopher
C
Packard
Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
Brendan M
BM
Buckley
Department of Cardiology, Kanazawa Medical University, Uchinada, Japan. Electronic address: kajinami@kanazawa-med.ac.jp.
Kouji
K
Kajinami
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000368:Aged; D000483:Alleles; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D005260:Female; D005838:Genotype; D006331:Heart Diseases / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy; D020641:Polymorphism, Single Nucleotide; D017035:Pravastatin / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D020521:Stroke / Q000097:blood / Q000188:drug therapy
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin
ABCA1 gene; Heart disease risk reduction; Low-density lipoprotein cholesterol lowering response; Statins