Genetic variation in the human thrombomodulin promoter locus and prognosis after acute coronary syndrome

• Published in: Thrombosis research Vol. 113; no. 5; pp. 319 - 326
• Main Authors: Öhlin, Ann-Kristin, Holm, Johan, Hillarp, Andreas
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 2004; Elsevier Science
• Subjects: Acute coronary syndrome; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Blood and lymphatic vessels; Cardiac and Cardiovascular Systems; Cardiology. Vascular system; Case-Control Studies; Clinical Medicine; Coronary Disease - genetics; Coronary Disease - mortality; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; DNA - genetics; Female; Genetic Variation; Heart; Humans; Injuries of the limb. Injuries of the spine; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - mortality; Point Mutation; Polymorphism, Single-Stranded Conformational; Prognosis; Promoter Regions, Genetic; Prospective Studies; Risk Factors; Sequence Deletion; Survival Analysis; Thrombomodulin; Thrombomodulin - genetics; Traumas. Diseases due to physical agents; Myocardial infarction; TED; TM; SSCP; Thrombomodulin; Acute coronary syndrome; MI; CHD; Human; Prognosis; Cardiovascular disease; Locus; Myocardial disease; Coronary heart disease
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2004.03.010

Introduction: Endothelial thrombomodulin (TM) plays a critical role in both anticoagulation and antiinflammation. An impaired TM cofactor function or reduced TM gene expression could constitute a prethrombotic abnormality leading to acute coronary events. Mutations in the TM gene occur, but their functional consequences on the expression and activity of the gene are not yet fully understood. Materials and methods: We performed a prospective study investigating the prevalence of TM mutations in the promoter region in 182 patients with acute coronary syndrome as well as in a control group. The patients were followed-up after 30 days and after 2 years for acute myocardial infarction (MI) and mortality. Results and conclusions: We identified 10 point mutations and 2 small deletions: −1861 C/A, −1852 C/G, −1803 G/C, −1752 G/C, −1213/1212 delTT, −1089 C/G, −1088 C/T, −1083/1082 delCC, −1066 A/C, −801 C/G, −651 A/C and −52 G/A. Two of the mutations, −1752 G/C and −1213/1212 delTT, were frequent in the patients as well as in the controls, while all the others were rare. The only significant finding was that both −1752 G/C and −1213/1212 delTT were associated with a lower than normal risk of suffering a clinical event among smokers at 30 days and 2 years. We did not gain any support for the hypothesis that TM mutations confer an increased risk of MI or mortality.