Abstract
Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins.
Highlights
Cerebrovascular disease (CVD) is characterized by brain ischemia that results in focal, acute neurological deficits and remains the fifth leading cause of death in the United States [1]
At least twenty-five different matrix metalloproteinases (MMPs) have been identified [29]. Members of this protease family have been divided into five subclasses based on structural similarity and substrate specificity that include the following: collagenases (MMP-1, MMP-8, and MMP-13) [30,31,32], gelatinases (MMP-2 and MMP-9) [33,34,35], stromelysins (MMP-3 and MMP-10) [36,37], metalloelastases [38,39], membrane-type MMPs (MT-MMP, MMP-14, MMP 15, MMP-16, MMP-17, MMP-24, and MMP-25) [40,41,42,43,44,45], and others (MMP-7, MMP-11, MMP-12, MMP-19, MMP-20 and MMP-23) [46,47]
Similar to other MMPs, MMP-12 polymorphisms have been found to play a role in the development of carotid atherosclerosis, which may be a potential mechanism in the association between certain alleles and ischemic stroke (IS) incidence
Summary
Cerebrovascular disease (CVD) is characterized by brain ischemia that results in focal, acute neurological deficits and remains the fifth leading cause of death in the United States [1]. Epidemiological studies highlight significant racial disparities with blacks having significantly higher stroke incidence compared to whites [6], younger age of incidence [7], and poorer functional outcomes [8]. High-density lipoprotein cholesterol and smoking in blacks, systolic blood pressure in Asians, and age in both Hispanics and blacks resulted in different atherosclerotic disease progression compared to whites [11]. Significant research has been carried out to establish the relationship between functional variants of different genes and IS risk [15,16,17,18,19,20,21] One such potential genetic risk factor may be matrix metalloproteinase (MMP) polymorphisms [22]. This review will evaluate MMP polymorphisms and provide some insight into their roles in IS incidence and clinical outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
