Versmissen J, Oosterveer DM, Yazdanpanah M, et al. A frequent variant in the ABCA1 gene is associated with increased coronary heart disease risk and a better response to statin treatment in familial hypercholesterolemia patients. Eur Heart J 2010 Jul 1. [Epub ahead of print]
pmid 20595220
doi: 10.1093/eurheartj/ehq208
http://eurheartj.oxfordjournals.org/content/early/2010/06/30/eurheartj.e...
http://eurheartj.oxfordjournals.org/content/early/2010/06/30/eurheartj.e...
http://eurheartj.oxfordjournals.org/content/early/2010/06/30/eurheartj.e...
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A frequent variant in the ABCA1 gene is associated with increased coronary heart disease risk and a better response to statin treatment in familial hypercholesterolemia patients
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Jorie Versmissen1, Daniëlla M. Oosterveer1, Mojgan Yazdanpanah1, Monique Mulder1, Abbas Dehghan2, Joep C. Defesche3, John J.P. Kastelein3 and Eric J.G. Sijbrands1,*
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Author Affiliations
. 1Department of Internal Medicine, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
. 2Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands
. 3Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
. *Corresponding author. Tel: +31 10 703 9222, Fax: +31 10 703 3639, Email: e.sijbrands@erasmusmc.nl
Received February 19, 2010.
Revision received April 29, 2010.
Accepted May 25, 2010.
Abstract
Aims Statins are essential for the reduction of risk of coronary heart disease (CHD) in familial hypercholesterolemia (FH). One of many genes influenced by statin treatment is the ATP-binding cassette transporter A1 (ABCA1) gene, which plays an important role in metabolism of high-density lipoprotein (HDL). The present aim was to test if the ABCA1 C69T polymorphism influences CHD risk and response to statin treatment.
Methods and results In a large cohort of 1686 FH patients without a history of CHD before 1 January 1990, we analysed statin-ABCA1 C69T polymorphism interaction by comparing treated and untreated patients. We used a Cox proportional hazard model adjusted for sex, birth year, and smoking. In analyses restricted to untreated patients, the TT genotype was associated with 1.7 times higher CHD risk than the CC genotype (hazard ratio (HR) =1.65, 95% confidence interval (95% CI): 1.08–2.53; P = 0.02). Conversely, in statin-treated FH patients, CHD risk in TT individuals was not increased (HR: 0.65, 95% CI: 0.35–1.24; P = 0.2). Formal testing confirmed this interaction (P = 0.03). HDL-cholesterol levels were significantly more raised in statin-treated patients with the TT than with the CC genotype (two-way ANOVA, P = 0.045).
Conclusion In untreated FH patients, the TT genotype of the ABCA1 C69T polymorphism was associated with increased CHD risk. However, in statin-treated patients, CHD risk was no longer significantly different between genotypes, at least partially explained by a higher rise in HDL-cholesterol levels during statin treatment in TT individuals.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010.