Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases

Abstract

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.

The role of the extracellular matrix in primary myelofibrosis

“…MMPs are a family of zinc-dependent endopeptidases and function in remodeling the ECM by its ability to degrade and cleave ECM components with wide substrate specificities. 93 For instance, MMP2 and MMP9 are effective in degrading collagen and gelatine structures in the ECM. 93 In addition, by producing MMP9, mature MKs are able to free themselves from the BM matrix at the osteoblastic niche and travel to the vascular niche.…”

“… 93 For instance, MMP2 and MMP9 are effective in degrading collagen and gelatine structures in the ECM. 93 In addition, by producing MMP9, mature MKs are able to free themselves from the BM matrix at the osteoblastic niche and travel to the vascular niche. In patients with PMF, MMPs are downregulated while tissue inhibitors of MMPs (TIMP) are increased.…”

Association of MMP-2 -753C>T and MMP-9 -1562C>T Polymorphisms with Chronic/Aggressive Periodontitis Risk: A Systematic Review and Meta-Analysis

“…MMP-2 gene encodes a protein that involved in the breakdown of ECM in normal physiological processes, such as embryonic development, reproduction and tissue remodeling (15). MMP-9 gene (also known as 92-kDa gelatinase or type V collagenase) is located on human chromosome 20q11.2–q13.1 (16). MMP-9 encodes a multidomain enzyme, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the ECM (16,17).…”

“…MMP-9 gene (also known as 92-kDa gelatinase or type V collagenase) is located on human chromosome 20q11.2–q13.1 (16). MMP-9 encodes a multidomain enzyme, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the ECM (16,17). In the past decade, several epidemiologic studies have been investigated the association of MMP-9 -1562C>T (rs3918242) and MMP-2 -753C>T (rs2285053) polymorphisms with susceptibility to periodontitis (8,10,11).…”

Assoziation hypertropher Post‐Akne‐Narben mit Einzelnukleotid‐Polymorphismus (rs243865) im Matrix‐Metalloproteinase‐2‐Gen

“…Acne vulgaris ist weltweit eine der häufigsten Dermatosen Matrix-Metalloproteinasen (MMPs), Zink-abhängige Endopeptidasen, und Tissue Inhibitors of Metalloproteinases (TIMPs), Regulatoren der MMP-Aktivität [26], spielen eine wichtige Rolle beim Umbau der ECM und es wurde vermutet, dass ein Ungleichgewicht zwischen ihnen zur Narbenbildung führt. Die Polymorphismen von MMP-2 und TIMP-2 wurden bereits bei verschiedenen Erkrankungen, einschließlich Karzinomen, Leukämien, ischämischen Herzerkrankungen, und arterieller Hypertonie, untersucht; sie führen zu einer geringeren Expression der jeweiligen Proteine [27][28][29][30][31]. Es gibt allerdings nur wenige Studien, die sich mit ihrer Expression bei dermatologischen Erkrankungen befassten [21,26].…”