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Thrombomodulin gene proximal promoter polymorphisms in premature acute coronary syndrome patients in Bahrain

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Thrombomodulin is expressed on endothelial cells and monocytes (mTM) where it has an anticoagulant function. Enzymatic cleavage from the cell surface produces soluble thrombomodulin (sTM) in plasma. Abnormal levels of sTM and mutations in the thrombomodulin gene (THBD) are linked to cardiovascular disease. The aim of this study was to investigate THBD proximal promoter mutations and levels of sTM and mTM in men presenting with premature acute coronary syndrome (ACS). This prospective cross-sectional study included 100 adult men with premature ACS (age <55 years) and 60 healthy age-matched controls. Plasma sTM was assayed by ELISA. mTM expression was assessed by flow cytometry with CD141 antibody. The −33 G/A polymorphism was identified by PCR-restriction fragment length polymorphism analysis and the THBD proximal promoter region was sequenced. Significantly lower sTM (P < 0.001) and higher mTM (P < 0.001) were seen in ACS patients. Heterozygous THBD promoter polymorphisms −33 G/A and −9/−10 GG/AT were found in eight patients and five control individuals. In patients and control individuals, allele frequencies of A were 0.02 and 0.025, and that of AT were 0.025 and 0.017, respectively. There were no significant associations of these polymorphisms with ACS, sTM levels or mTM expression. THBD polymorphisms −33 G/A and −9/−10 GG/AT are present in low frequency in our patient population, and are more frequent in the South Asians as compared to the Arabs. The frequency of −33 G/A is lower, whereas that of −9/−10 GG/AT is higher than that reported in the Orientals. The presence of THBD proximal promoter polymorphisms do not explain variations in levels of sTM and mTM in this patient population.
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Keywords: Arab; South Asian; acute coronary syndrome; monocyte; polymorphism; thrombomodulin

Document Type: Research Article

Affiliations: 1: H.H. Princess Al-Jawhara Centre for Molecular Medicine, Genetics, and Inherited Disorders 2: Department of Pathology, College of Medicine and Medical Sciences 3: Department of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain 4: Department of Medical Laboratory Science, Kuwait University, Kuwait 5: Department of Internal Medicine, Salmaniya Medical Complex 6: Department of Family and Community Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain

Publication date: December 1, 2015

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