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

TLDR

Atherosclerosis is a chronic inflammatory disease of the blood vessels, and Toll‑like receptor 4 (TLR4) mediates 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. We conducted a case‑control study of 183 acute coronary syndrome patients and 216 controls, screening 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 (adjusted OR 0.41, 95 % CI 0.18–0.95) and, in controls, with lower plasma fibrinogen and soluble VCAM‑1 levels, supporting an association between the Asp299Gly polymorphism and acute coronary syndromes.

Abstract

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.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).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.