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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:e61.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Association of the Toll-Like Receptor 4 Gene Asp299Gly Polymorphism With Acute Coronary Events

Nejma Ameziane; Tiphaine Beillat; Patrice Verpillat; Sylvie Chollet-Martin; Marie-Claude Aumont; Patrick Seknadji; Maryse Lamotte; Dominique Lebret; Véronique Ollivier; Dominique de Prost

From INSERM U479 (N.A., S.C-M., D.P., V.O.), Faculté Xavier Bichat, Paris; Département de Santé Publique (P.V.), Hôpital Louis Mourier, AP-HP, Colombes; Service d’Hématologie Biologique et Immunologie et FGC de génétique (N.A., M.L., D.L., D.P.), Hôpital Louis Mourier, AP-HP, Colombes; and Service de Cardiologie A (P.S., M.C.A.), Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.

Correspondence to Dominique de Prost, Service d’Hématologie Biologique et d’Immunologie, Hôpital Louis Mourier, 178 rue des Renouillers, 92701 Colombes Cédex, France. E-mail dominique.de-prost{at}lmr.ap-hop-paris.fr

Objective— Atherosclerosis is a chronic inflammatory disease of the blood vessels. Toll-like receptor 4 (TLR4) is a transmembrane receptor that is involved in mediating inflammatory responses to bacterial endotoxin and other ligands. The aim of this study was to search for an association between a common functional polymorphism of TLR4 —Asp299Gly—and acute coronary syndrome.

Methods and Results— We conducted a case-control study of 183 patients with acute coronary syndromes and 216 controls. We screened the TLR4 gene for the Asp299Gly polymorphism using a 5' fluorogenic assay. The 299Gly allele was associated with a decreased risk of acute coronary events independently of standard coronary risk factors. The adjusted odds ratio associated with this allele was 0.41 (95% CI, 0.18 to 0.95; P=0.037). In controls, TLR4 heterozygosity was also associated with a significant decrease in plasma fibrinogen and soluble vascular cellular adhesion molecule-1 levels (P<0.01).

Conclusions— These results, which must be confirmed by a prospective longitudinal study, provide evidence of an association between the Asp299Gly polymorphism of the human TLR4 receptor and acute coronary syndromes. They confirm the previously reported involvement of TLR4 in carotid and femoral artery atherosclerosis.

Key Words: TLR4 • acute coronary events • genetics

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