Association of matrix metalloproteinase-3 gene 5A/6A polymorphism with the recurrence of ischemic stroke: A prospective observational study

Abstract

Studies have demonstrated that matrix metalloproteinase-3 (MMP-3) is involved in the development and progression of atherosclerosis. However, there is no information available on the association of MMP-3 5A/6A polymorphism with recurrent ischemic stroke (IS) in different IS subtypes. We investigated the potential associations between MMP-3 serum level and −1171 5A/6A polymorphism and the recurrence of IS in a Chinese population. Consecutive acute first-ever IS patients were enrolled between August 2008 and October 2013. The genotypes of MMP-3 5A/6A polymorphism were determined using polymerase chain reaction-restriction fragment length polymorphism. IS recurrence was monitored after the index event and multivariate Cox proportional hazards model was constructed to identify factors related to future IS recurrence. A total of 1282 eligible patients were enrolled. During a 2-year follow-up period, 157 (12.25%) patients had recurrent events. MMP-3 level was significantly higher in patients with 5A/6A or 5A/5A genotype (22.72±7.29ng/ul) than in patients with 6A/6A genotype (20.48±7.58ng/ul), P<0.001. No interaction between MMP-3 5A/6A polymorphism and the risk of recurrence in total IS patients was found. The variant 5A/6A+5A/5A genotype and the 5A allele were significantly associated with a high risk of recurrence for large-artery atherosclerosis (LAA) (multivariate-adjusted, P=0.002, 0.001, respectively), but not for small-artery occlusion and cardioembolism. Our finding showed that MMP-3 5A/6A may be a useful biomarker for predicting recurrence for LAA stroke patients and 5A allele carrier may bear a higher risk of recurrence among patients with the subtype of LAA.