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A mutation in the thrombomodulin gene, (127)G to a coding for Ala25Thr, and the risk of myocardial infarction in men

Doggen, CJM; Kunz, G; Rosendaal, FR; Lane, DA; Vos, HL; Stubbs, PJ; ... Ireland, H; + view all (1998) A mutation in the thrombomodulin gene, (127)G to a coding for Ala25Thr, and the risk of myocardial infarction in men. THROMB HAEMOSTASIS , 80 (5) 743 - 748.

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Abstract

Thrombomodulin is an endothelial cell surface receptor that transforms the procoagulant thrombin into an anticoagulant. A mutation in the thrombomodulin gene is a potential risk factor for venous and arterial thrombosis.We screened a region within the coding sequence of the thrombomodulin gene by single-strand conformation polymorphism analysis (SSCP) in a pilot study of 104 patients with myocardial infarction and 104 age, sex and race matched controls. We identified a (127)G to A mutation in the gene, which predicts an Ala25Thr substitution, in 2 out of 104 patients (1 man and 1 woman) with myocardial infarction but in no controls. We assessed the risk of myocardial infarction associated with the mutation in a larger "Study of Myocardial Infarctions Leiden" (SMILE). Among 560 men with a first myocardial infarction before the age of 70, 12 were carriers of the Ala25Thr substitution. In a control group of 646 men, frequency-matched for age, seven were carriers of the Ala25Thr substitution. The allelic frequencies were 1.07% among patients and 0.54% among controls suggesting risk associated with the mutation [odds ratio (OR) 2.0, 95% confidence interval (CI) 0.8-5.1]. In patients aged below 50, the predicted risk was almost seven times increased (OR 6.5, CI 0.8-54.2). In the presence of additional risk factors, such as smoking and a metabolic risk factor, the predicted risk increased to 9-fold (OR 8.8, CI 1.8-42.2) and 4-fold (OR 4.4, CI 0.9-21.3), respectively.While not conclusive, these results strongly suggest that the Ala25Thr substitution is a risk factor for myocardial infarction, especially in young men, and when in the presence of additional risk factors.

Type:Article
Title:A mutation in the thrombomodulin gene, (127)G to a coding for Ala25Thr, and the risk of myocardial infarction in men
Keywords:ACTIVATED PROTEIN-C, AMINO-ACID DIMORPHISM, VENOUS THROMBOSIS, THROMBOEMBOLIC-DISEASE, YOUNG-WOMEN, THROMBOPHILIA, SUBCOMMITTEE, COAGULATION, DEFICIENCY, RESISTANCE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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