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

Abstract

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 ≥1I 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. © 2005 International Society on Thrombosis and Haemostasis.