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.
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 humanTLR4 receptor and acute coronary syndromes. They confirm the previously reported involvement of TLR4 in carotid and femoral artery atherosclerosis.
Authors: Mamoona Noreen; Muhammad Ali A Shah; Sheeba Murad Mall; Shazia Choudhary; Tahir Hussain; Iltaf Ahmed; Syed Fazal Jalil; Muhammad Imran Raza Journal: Inflamm Res Date: 2012-01-26 Impact factor: 4.575
Authors: Kathrin S Michelsen; Michelle H Wong; Prediman K Shah; Wenxuan Zhang; Juliana Yano; Terence M Doherty; Shizuo Akira; Tripathi B Rajavashisth; Moshe Arditi Journal: Proc Natl Acad Sci U S A Date: 2004-07-12 Impact factor: 11.205
Authors: Cameron R Stewart; Lynda M Stuart; Kim Wilkinson; Janine M van Gils; Jiusheng Deng; Annett Halle; Katey J Rayner; Laurent Boyer; Ruiqin Zhong; William A Frazier; Adam Lacy-Hulbert; Joseph El Khoury; Douglas T Golenbock; Kathryn J Moore Journal: Nat Immunol Date: 2009-12-27 Impact factor: 25.606