Identification of Genetic Aberrations in Thrombomodulin Gene in Patients With Recurrent Venous Thromboembolism

Ahmad, Abrar; Sundquist, Kristina; Zöller, Bengt; Svensson, Peter; Sundquist, Jan; Memon, Ashfaque A.

doi:10.1177/1076029616686716

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…The Malmö thrombophilia study (MATS) is a well-characterized cohort including 1465 VTE patients that were followed after inclusion in this study (March 1998) until VTE recurrence or death or the end of the study (December 2008) (30, 31). This study was performed at Skåne University Hospital Malmö, Sweden.…”

Section: Methodsmentioning

confidence: 99%

Fat mass and obesity-associated gene rs9939609 polymorphism is a potential biomarker of recurrent venous thromboembolism in male but not in female patients

Ahmad

Memon

Sundquist

et al. 2018

Gene

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Multiple genetic variations have been identified in FTO (fat mass and obesity-associated) gene. Among them, FTO rs9939609 polymorphism is shown to be associated with the risk of primary venous thromboembolism (VTE). However, its role in recurrent VTE is not known. The aim of our study was to investigate the association between FTO rs9939609 polymorphism and the risk of VTE recurrence in a prospective follow-up study in both male and female patients. FTO rs9939609 polymorphism (T/A) was analyzed in the Malmö thrombophilia study (MATS, followed for ~10 years) by using TaqMan PCR. MATS patients (n = 1050) were followed from the discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of follow-up. A total of 126 patients (12%) had VTE recurrence during follow-up. Cox regression analyses showed that sex modified the potential effect of FTO rs9939609 polymorphism on VTE recurrence. Male patients with the AA genotype for the FTO rs9939609 polymorphism had significantly higher risk of VTE recurrence as compared to the TT or AT genotypes (univariate hazard ratio [HR] = 2.05, 95% confidence interval [CI] = 1.2-3.5, P = 0.009 and adjusted HR = 2.03, 95% CI 1.2-3.6, P = 0.013). There was no association between FTO rs9939609 polymorphism and VTE recurrence in female patients. In conclusion, our results show that FTO rs9939609 polymorphism in recurrent VTE may differ according to gender and FTO polymorphism may predict VTE recurrence in male patients.

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Section: Methodsmentioning

confidence: 99%

Fat mass and obesity-associated gene rs9939609 polymorphism is a potential biomarker of recurrent venous thromboembolism in male but not in female patients

Ahmad

Memon

Sundquist

et al. 2018

Gene

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“…In patients with VTE, a series of clinical studies addressed the role of sporadic mutations and polymorphisms in the TM gene [71]. In these studies, genetic variation in the promoter, coding region, and 3 -untranslated regions (3 -UTR) of the TM gene were considered [72,73]. Although some studies suggested a role for THBD variants, results are conflicting.…”

Section: Thrombomodulinmentioning

confidence: 99%

Rare Defects: Looking at the Dark Face of the Thrombosis

D’Andrea

Margaglione

2021

IJERPH

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Venous thromboembolism (VTE) constitutes a serious and potentially fatal disease, often complicated by pulmonary embolism and is associated with inherited or acquired factors risk. A series of risk factors are known to predispose to venous thrombosis, and these include mutations in the genes that encode anticoagulant proteins as antithrombin, protein C and protein S, and variants in genes that encode instead pro-coagulant factors as factor V (FV Leiden) and factor II (FII G20210A). However, the molecular causes responsible for thrombotic events in some individuals with evident inherited thrombosis remain unknown. An improved knowledge of risk factors, as well as a clear understanding of their role in the pathophysiology of VTE, are crucial to achieve a better identification of patients at higher risk. Moreover, the identification of genes with rare variants but a large effect size may pave the way for studies addressing new antithrombotic agents in order to improve the management of VTE patients. Over the past 20 years, qualitative or quantitative genetic risk factors such as inhibitor proteins of the hemostasis and of the fibrinolytic system, including fibrinogen, thrombomodulin, plasminogen activator inhibitor-1, and elevated concentrations of factors II, FV, VIII, IX, XI, have been associated with thrombotic events, often with conflicting results. The aim of this review is to evaluate available data in literature on these genetic variations to give a contribution to our understanding of the complex molecular mechanisms involved in physiologic and pathophysiologic clot formation and their role in clinical practice.

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“…In contrast, inherited deficiency of thrombomodulin activity typically causes late-onset large vessel or coronary thrombosis, 258 if it causes any disease at all. 259 That is not to question the benefit of expressing human thrombomodulin in xenografts. Transgenic expression of human thrombomodulin is certainly more convenient and less toxic than administration of anticoagulant agents (or correction of what we think might be the more fundamental problem with complement regulation).…”

Section: Physiological and Biochemical Barriers To Xenotransplantatiomentioning

confidence: 99%

Xenotransplantation: Progress Along Paths Uncertain from Models to Application

2018

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For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because scarcity of human tissues limited allotransplantation to a fraction of those who could benefit. In principle, use of animals such as pigs as a source of transplants would allow transplantation to exert a vastly greater impact than allotransplantation on medicine and public health. However, biological barriers to xenotransplantation, including immunity of the recipient, incompatibility of biological systems, and transmission of novel infectious agents, are believed to exceed the barriers to allotransplantation and presently to hinder clinical applications. One way potentially to address the barriers to xenotransplantation is by genetic engineering animal sources. The last 2 decades have brought progressive advances in approaches that can be applied to genetic modification of large animals. Application of these approaches to genetic engineering of pigs has contributed to dramatic improvement in the outcome of experimental xenografts in nonhuman primates and have encouraged the development of a new type of xenograft, a reverse xenograft, in which human stem cells are introduced into pigs under conditions that support differentiation and expansion into functional tissues and potentially organs. These advances make it appropriate to consider the potential limitation of genetic engineering and of current models for advancing the clinical applications of xenotransplantation and reverse xenotransplantation.

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Identification of Genetic Aberrations in Thrombomodulin Gene in Patients With Recurrent Venous Thromboembolism

Abstract: Abstract:Introduction: Thrombomodulin (THBD) serves as a cofactor for thrombin-mediated activation

Cited by 6 publications

References 49 publications

Fat mass and obesity-associated gene rs9939609 polymorphism is a potential biomarker of recurrent venous thromboembolism in male but not in female patients

Fat mass and obesity-associated gene rs9939609 polymorphism is a potential biomarker of recurrent venous thromboembolism in male but not in female patients

Rare Defects: Looking at the Dark Face of the Thrombosis

Xenotransplantation: Progress Along Paths Uncertain from Models to Application

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