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Coagulopathy in Type 2 Diabetes Mellitus: Pathological Mechanisms and the Role of Factor XIII-A Single Nucleotide Polymorphisms

[ Vol. 15 , Issue. 6 ]

Author(s):

Marry-ann Ntanyane Phasha, Prashilla Soma , Etheresia Pretorius and Alia Phulukdaree *   Pages 446 - 455 ( 10 )

Abstract:


The prevalence of type 2 diabetes mellitus (T2DM) has quadrupled within three decades since 1980, affecting 422 million adults in 2016. It remains one of the most common noncommunicable chronic diseases and the underlying risk factor for cardiovascular diseases worldwide. There are different underlying mechanisms that play a role in the development of pathologies associated with the disease such as hyperglycaemia, oxidative stress, obesity, inflammation and hypercoagulation; each of which are interlinked. Hyperglycaemia, oxidative stress and obesity play a huge role in the activation of inflammation and coagulation. Activation of inflammatory pathways increases the production of thrombin which predisposes the development of thrombotic related diseases. One of the factors that contribute to the increase of thrombin is the impairment of the fibrinolysis process due to decreased expression of tissue-plasminogen activator (tPA) by increased levels of plasminogen activator inhibitor-1 (PAI-1). Coagulation factor XIII (FXIII), a transglutaminase that is composed of subunits A and B (FXIII-A2B2), is essential for the last step of fibrin clot formation in the coagulation pathway. Genetic variation of FXIII-A in the form of single nucleotide polymorphisms (SNPs) alters the activity of FXIII, altering clot properties which influence disease outcomes. This review discusses the link between underlying mechanisms of T2DM, well known FXIII-A variants and coagulation.

Keywords:

Type 2 diabetes mellitus, coagulation, factor XIII, single nucleotide polymorphisms, pathological, mechanisms.

Affiliation:

Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, Department of Physiological Science, Faculty of Sciences, Stellenbosch University, Pretoria, Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria



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