Maral Senem, Acar Muradiye, Balcik Ozlem Sahin, Uctepe Eyyup, Hatipoglu Omer Faruk, Akdeniz Derya, Altun Hatice Uludag, Kosar Ali, Gunduz Mehmet, Gunduz Esra
From the Department of Internal Medicine (SM, DA); Division of Hematology (OSB, AK); Department of Medical Genetics (MA, EU, OFH, MG, EG); Department of Medical Microbiology (HUA); and Department of Otolaryngology (MG), Turgut Özal University Faculty of Medicine, Ankara, Turkey.
Medicine (Baltimore). 2015 Apr;94(16):e732. doi: 10.1097/MD.0000000000000732.
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.
真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化等慢性骨髓增殖性疾病源于骨髓中肿瘤干细胞的克隆性增殖。基质金属蛋白酶(MMPs)是一类锌依赖性内肽酶,具有降解所有类型细胞外基质(ECM)的潜力,并且在ECM重塑中也发挥作用。已知MMPs在骨髓重塑中起作用。我们研究的主要目的是探讨慢性骨髓增殖性疾病与某些MMP基因多态性之间的关系。这种关系的证明将有助于了解这些多态性是否可能是疾病潜在的早期诊断标志物。
2010年12月至2011年5月期间,从土耳其安卡拉图尔古特·奥扎尔大学医院门诊选取患者。28例先前诊断并随访的PV患者、17例继发性红细胞增多症(SP)患者和12例ET患者以及22名健康人的对照组被纳入研究。
从外周血中分离DNA。使用聚合酶链反应-限制性片段长度多态性方法,通过琼脂糖凝胶电泳分析MMP2和MMP9基因多态性。在MMP9的Gln279Arg多态性率方面,研究组与对照组之间存在统计学显著差异。ET组中观察到最高的MMP9 Gln279Arg多态性率。但对照组中没有人具有多态性MMP9。在MMP2 - 735 C>T多态性率方面,各组之间没有统计学显著差异。
总之,MMP9基因Gln279Arg多态性与ET、SP和PV疾病相关。因此,我们认为这些基因多态性可能在骨髓纤维化机制中起作用,并且可能是增加血栓形成风险的一个因素。阐明MMP - 血栓形成和MMP - 纤维化之间关系的分子基础,能更好地理解PV和ET疾病的病理生理学,并将为诊断和治疗带来新方法。