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on April 16, 2009

Stroke. 2009
Published online before print April 16, 2009, doi: 10.1161/STROKEAHA.108.537159
A more recent version of this article appeared on June 1, 2009
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Submitted on September 10, 2008
Revised on October 23, 2008
Accepted on November 13, 2008

Fractalkine Receptor/Ligand Genetic Variants and Carotid Intima-Media Thickness

Stéphanie Debette MD, PhD*; Steve Bevan BSc, PhD; Jean-François Dartigues MD, PhD; Matthias Sitzer MD; Matthias Lorenz MD; Pierre Ducimetière PhD; Philippe Amouyel MD, PhD; and Hugh S. Markus MD, FRCP

Clinical Neuroscience (S.D., S.B., H.S.M.), St George's University of London, UK; the Department of Neurology (EA2691) (S.D.), Lille University-Hospital; Inserm, U744 (S.D., P.A.), Pasteur Institute, Lille; Inserm, U593 (J.F.D.), Bordeaux; Inserm, U909 (P.D.), Paris, France; the Department of Neurology (M.S., M.L.), J.W. Goethe University, Frankfurt/Main, Germany.

* To whom correspondence should be addressed. E-mail: stephdebette{at}wanadoo.fr.

Background and Purpose—The fractalkine ligand/receptor (CX3CL1/CX3CR1) complex is important in inflammatory responses and has been associated with vascular disease. We determined whether genetic variants in CX3CL1 and CX3CR1 are associated with carotid atherosclerosis in 2 large European populations.

Methods—18 polymorphisms in CX3CL1 and CX3CR1 were genotyped in 2763 German community individuals (CAPS). Positive results were tested for replication on 6049 French community individuals (3C Study).

Results—In CAPS we found associations of common carotid artery (CCA)-IMT with 2 CX3CL1 (rs170364, rs614230) and 1 CX3CR1 (rs3732378) variants, and significant interactions of CX3CR1 rs11129820, rs3732378, and rs614230 variants with smoking and alcohol consumption in relation with CCA-IMT. None of these were replicated in 3C. In 3C only there was a borderline significant association of rs3732378 with carotid plaques.

Conclusion—In almost 9000 subjects, we found no replicable associations of CX3CL1 and CX3CR1 polymorphisms with CCA-IMT or plaque.
Key words: atherosclerosis • carotid intimal medial thickness • carotid ultrasound • epidemiology • genetics • risk factors • ultrasound • carotid artery






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