5A/6A polymorphism of the stromelysin-1 gene and angiographic restenosis after coronary artery stenting

Background: Coronary stent deployment is a major advance in interventional treatment, but 20-40% of patients still develop in-stent restenosis (ISR) due to neointimal hyperplasia. Genetic factors play a role in restenosis. This study investigated the frequency of 5A/6A polymorphism in the promoter of the stromelysin-1 gene, and the issue of whether it contributes to restenosis among patients receiving coronary stent in the Chinese population in Taiwan. Methods: We investigated 344 symptomatic patients after successful coronary stent placement. All patients received repeated angiography after 6 months, or earlier if clinically indicated. Angiographic restenosis was defined as ≥ 50% diameter stenosis at follow-up. Genotyping for stromelysin-1 promoter was based on a polymerase chain reaction technique. Results: The stromelysin-1 gene promoter genotypes 5A5A, 5A6A, and 6A6A were distributed in 3.5%, 22.7%, and 73.8% of patients, respectively. The frequency of the 6A allele was 0.85. There was no significant difference in angiographic ISR between the non-6A6A and 6A6A groups (28.9% and 37.0%, respectively, p = 0.165). However, subgroup analysis revealed a significant difference in patients according to angina status. Among the 5A5A and 5A6A genotype groups, patients with unstable angina had significantly higher ISR rates than those with stable angina (48% vs 21.5%, p = 0.013). On the other hand, among patients with stable angina, those with a 6A6A genotype had a higher ISR rate than those with a non-6A6A genotype (p = 0.029), making the 6A6A genotype an independent predictor of ISR (odds ratio, 2.57; 95% confidence interval, 1.22-5.41; p = 0.013). Conclusion: There is a low frequency of the stromelysin-1 promoter 5A allele in the Chinese population in Taiwan. How stromelysin-1 5A/6A polymorphism affects ISR appears to be linked to angina status. These results merit further study to identify patients carrying genotypes which put them at increased risk of ISR, and which matrix metalloproteinase inhibitors or drug-eluting stents are more effective for those at risk.