Association of MMP-8 polymorphisms with tendinopathy of the primary posterior tibial tendon: a pilot study

Tendon disorders are common and are treated on a daily basis in orthopedic foot and ankle practices. Some tendons are particularly vulnerable to primary degenerative changes, such as the patellar, Achilles, rotator cuff, biceps, posterior tibial, and fibular tendons. Significant advances in histopathology and research imaging techniques have contributed to an improved understanding of the pathophysiology of tendon degeneration. However, both mechanical factors and vascular and neurological disorders have limitations in explaining the etiology of many cases. It is known that intense physical activity may predispose an individual to tendinopathy, but some individuals have a predisposition with no clinically recognized cause. The literature suggests that individual characteristics, including genetic inheritance, may influence the likelihood of developing tendinopathy. Thus, there is a group of individuals with a genetic background that causes increased susceptibility to diseases of the tendon. Matrix metalloproteinases (MMPs) are a pivotal family of zinc-dependent enzymes responsible for the degradation of extracellular matrix components, including basement membrane collagen, interstitial collagen, fibronectin and various proteoglycans, during normal remodeling, repair processes, development and inflammation. MMPs are expressed in response to specific stimuli by resident connective tissue cells and by the major inflammatory cell types that invade tissues during remodeling events, including tendinopathy. MMP-8, or collagenase-2, was initially discovered in neutrophils, in which it was thought to be exclusively produced, but this enzyme was subsequently shown to be expressed by a variety of other cell types, including endothelial cells, smooth muscle cells, macrophages, polymorphonuclear leukocytes, gingival fibroblasts, keratinocytes, chondrocytes, odontoblasts and oral cancer cells. It has been suggested that MMP-8 degrades type I collagen, thereby contributing to tissue degradation and remodeling. MMP-8 is an important mediator of tissue destruction in several inflammatory diseases and is related to cardiovascular disease, bronchiectasis, pulmonary insufficiency, periodontitis, melanoma, cancer of the head and neck, and diabetic wound healing. The MMP-8 gene, located on chromosome 11, contains functional polymorphisms in the promoter region, including the substitution of a cytosine by a thymine at position 799 (rs11225395). Alterations in this gene have been associated with chronic dilatation of the bronchi13 and breast cancer. The discovery of genetic markers of tendinopathy risk could allow for the identification of susceptible individuals and, thus, early therapeutic interventions. MMPs play key roles in tissue destruction and may have important roles in the pathogenesis of tendinopathy. Therefore, we hypothesized that the -799C/T polymorphism in MMP-8 was associated with tendinopathy of the primary posterior tibial tendon and could be a risk factor for this condition.