Background Coronary artery disease is one of the leading causes of mortality and morbidity around the world. The Indo-Pak sub-Continent has one of the highest predispositions to Coronary artery disease. Apart from the established risk factors such as diabetes mellitus, hypertension, smoking, alcohol intake, family history, and obesity that played an important role in the development of CAD, genetic polymorphism also emerge as a risk factor in the incidence of Coronary artery disease. Thrombomodulin (THBD) gene is one of them. It is a transmembrane protein expressed on the surface of endothelial cells. It is an important vasoprotective and thromboresistant substance. This natural anticoagulant abates thrombin’s activity and activates Protein C. The relationship between Thrombomodulin gene polymorphisms and coronary disease remains Controversial. It has been reported that a single nucleotide polymorphism (CT) at position 1418 of thrombomodulin gene results in amino acid change from alanine (A) to valine (V) at protein position 455 of TM gene (Ala 455 Val). A considerable number of studies conducted across the globe showed a varied relationship between TM gene polymorphism and coronary artery disease. Therefore the aim of the present study is to assess the association between TM gene Polymorphism and coronary artery disease in general adult Population of Karachi, Pakistan ii METHODOLOGY This is a case control study that was conducted in Tabba Heart Institute in association with National Institute of Blood Disease, Karachi. In this study we explore the association between C/T dimorphism that might predict as a risk factor for coronary artery disease in population of Karachi. We compared C/T dimorphism in 92 cases with 90 control subjects by allele specific amplification. RESULTS The frequency of CC, CT and TT genotype was 81 (90 %), 6 (6.7%) 3 (3.3%) in controls and 67 (72.8%), 20 (21.7%) and 5 (5.4%) in cases respectively. In case group the CT/TT genotype were found to be significantly associated with coronary artery diseases when compared with control group (p-value 0.009). Both cases and control were in Hardy Weinberg equilibrium (HWE), i.e. for cases HWE was (X2 = 3.81, p>0.05) and for controls HWE was (X2 = 19.4, p>0.05). CONCLUSION TM C1418T polymorphism appears as a risk marker in Coronary Artery Disease patients in the population of Karachi, Pakistan.
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