on June 1, 2006
Published online before print June 1, 2006, doi: 10.1161/01.STR.0000226565.76113.6c
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Submitted on November 10, 2005
From the Department of Neurology and Stroke Centre (D.B., J.L., P.-J.T., P.A.), Bichat University Hospital, Denis Diderot University and Medical School, Paris, France; Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease (K.S.-P., S.-M.B.-H.), University of Muenster; Charité, University Medicine Berlin, Campus Benjamin Franklin, Institute for Clinical Pharmacology and Toxicology (J.S.), Berlin, Germany; INSERM U543 (C.C), Centre National du Genome (M.L.), INSERM 525 (O.P., F.C., C.P.), Pitié-Salpêtrière Medical School, Paris, France; and Department of Neurology, University of Arizona, Tucson (D.B.). * To whom correspondence should be addressed. E-mail: pierre.amarenco{at}bch.aphp.fr.
Background and Purpose--Carotid intima-media thickness (IMT) reflects generalized atherosclerosis and is predictive of future vascular events. Evidence exists that carotid IMT is heritable, and genetic studies can provide clues in the pathogenesis of atherosclerosis. Methods--We recruited 470 white ischemic stroke patients, measured common carotid artery (CCA) IMT, and analyzed 54 polymorphisms with suspected roles in atherosclerosis. Results--Among the polymorphisms tested, the angiotensin-converting enzyme insertion/deletion, osteopontin (OPN) T-443C, monocyte chemoattractant protein-1 (MCP-1) G-927C, and MCP-1 A-2578G polymorphisms were associated with CCA-IMT in age-gender-adjusted analysis. In multivariate analysis, the association between the OPN and MCP-1 polymorphisms remained significant. The OPN-443C allele was associated with increased IMT in the dominant model (0.053 mm for the TC and CC genotypes; P=0.001). The MCP-1-927C allele was associated with increased IMT in the additive model (0.040 mm for each C allele; P=0.001), and the MCP-1-2578 G allele was associated with decreased IMT in the recessive model (0.088 mm for the GG genotype; P=0.002). Conclusions--The OPN and MCP-1 genes, coding for 2 cytokines with known roles in atherosclerosis, may contribute to increased carotid IMT and warrant further study.
Revised on March 1, 2006
Accepted on March 15, 2006
Cytokine Polymorphisms Associated With Carotid Intima-Media Thickness in Stroke Patients
David Brenner MD;
Key words: intima-media thickness • genetics
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