Stromelysin‐1 promoter 5A/6A polymorphism is an independent genetic prognostic risk factor and interacts with smoking cessation after index premature myocardial infarction

• Published in: Journal of thrombosis and haemostasis Vol. 3; no. 9; pp. 1998 - 2005
• Main Authors: LIU, P.‐Y., LI, Y.‐H., TSAI, W.‐C., TSAI, L.‐M., CHAO, T.‐H., WU, H.‐L., CHEN, J.‐H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Inc 01.09.2005
• Subjects: acute myocardial infarction; Adult; Age of Onset; Alleles; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Female; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Male; matrix metalloproteinase; Matrix Metalloproteinase 3 - genetics; Middle Aged; Myocardial Infarction - epidemiology; Myocardial Infarction - genetics; polymorphism; Polymorphism, Genetic; Prognosis; Promoter Regions, Genetic - genetics; Risk Factors; Smoking Cessation; stromelysin‐1
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2005.01515.x

Objective: To evaluate the prognostic roles of multiple polymorphisms and smoking cessation for premature myocardial infarction (MI). Methods: We studied 170 patients with MI onset before the age of 45 years (range 27–45 years, 84% men) and analyzed the traditional risk factors and several candidate genes’ associations with their subsequent coronary events. Results: Follow‐up data were available for a total of 162 individuals (95.3%) with the other 38 individuals (4.7%) being lost‐to‐follow‐up premature MI patients. During a mean period of 4.43 years’ follow‐up, diabetes mellitus (DM), hypertension, hypercholesterolemia and Killip's status ≥II were more frequent among patients with subsequent cardiac events (all P‐values <0.05). The frequency of 5A allele of stromelysin‐1 gene was significantly higher among event group (P = 0.01). Smoking cessation after MI, use of β‐blocker or angiotensin‐converting enzyme inhibitor (ACEI) could improve outcome (all P‐values <0.05). After multivariate analysis, we found that DM was an independent risk factor for survival [Hazard ratio (HR) 2.45, P = 0.01]. Successful smoking cessation and therapy with ACEI could have a protective effect (HR 0.33 and 0.09, P = 0.01 and <0.01, respectively). The stromelysin‐1 5A gene polymorphism was also an independent survival predictor (HR 2.51, P = 0.03). In addition, smoking cessation could significantly modify the risk, especially among patients with 5A allele polymorphism (HR 6.75 vs. 1.50). Conclusion: We thus conclude that the stromelysin‐1 gene polymorphism alone or in combination with smoking cessation can influence the prognosis after index premature MI.