Common variants in the gene encoding ATP-binding cassette transporter 1 in men with low HDL cholesterol levels and coronary heart disease

Margaret E. Brousseau, Marek Bodzioch, Ernst J. Schaefer, Allison L. Goldkamp, Danuta Kielar, Mario Probst, Jose M. Ordovas, Charalampos Aslanidis, Karl J. Lackner, Hanna Bloomfield Rubins, Dorothea Collins, Sander J. Robins, Peter W F Wilson, Gerd Schmitz

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


HDL cholesterol (HDL-C) deficiency is the most common lipid abnormality observed in patients with premature coronary heart disease (CHD). Recently, our laboratory and others demonstrated that mutations in the ATP-binding cassette transporter 1 (ABCA1) gene are responsible for Tangier disease, a rare genetic disorder characterized by severely diminished plasma HDL-C concentrations and a predisposition for CHD. To address the question of whether common variants within the coding sequence of ABCA1 may affect plasma HDL-C levels and CHD risk in the general population, we determined the frequencies of three common ABCA1 variants (G596A, A2589G and G3456C) in men participating in the Veterans Affairs Cooperative HDL Cholesterol Intervention Trial (VA-HIT), a study designed to examine the benefits of HDL raising in men having low HDL-C (≤ 40 mg/dl) and established CHD, as well as in CHD-free men from the Framingham Offspring Study (FOS). Allele frequencies (%) in VA-HIT were 31, 16, and 4 for the G596A, A2589G, and G3456C variants, respectively, versus 27, 12, and 2 in FOS (P < 0.03). None of the variants were significantly associated with plasma HDL-C concentrations in either population; however, in VA-HIT, the G3456C variant was associated with a significantly increased risk for CHD end points, suggesting a role for this variant in the premature CHD observed in this population.

Original languageEnglish (US)
Pages (from-to)607-611
Number of pages5
Issue number3
StatePublished - Feb 15 2001

Bibliographical note

Funding Information:
The authors are grateful to Tatyana Massov and Judith R. McNamara of New England Medical Center for the plasma lipid analyses, as well as to Alison Kelleher of Tufts University for technical assistance. This work was supported by the Department of Veterans Affairs, Medical Research Services VA Cooperative Program, research grants of the Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany and by NIH grant R01 HL60935 and contract 53-19550-50-003 from the US Department of Agriculture Research Service.


  • ATP-binding cassette 1
  • Coronary heart disease
  • High density lipoproteins
  • Tangier disease


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