Abstract:
Diabetes is a metabolic disorder, characterized by recurrent or persistent hyperglycemia,
affecting body`s vital organs and resulting in life threatening complications. One of such
complications is coronary artery disease (CAD). It results in the constriction of arteries which
prevent blood from reaching the heart muscles, thereby, increasing strain on heart. Among
several candidate genes, endothelial nitric oxide synthase (eNOS) is known to play vital role
in the pathogenesis of diabetes and atherosclerosis. The two most studied single nucleotide
variants of eNOS gene are 786T/C and 894 G/T polymorphisms. This study was aimed to
investigate the association of 786T/C and 894G/T nucleotide polymorphisms of endothelial
nitric oxide synthase gene in type 2 diabetes and coronary artery disease patients from
Pakistan. Total sample size of 105 was grouped into 35 controls, 35 T2DM patients and 35
CAD plus T2DM patients. Allele specific PCR was carried out to investigate the effect of
786T/C polymorphism in cases and healthy controls. The genotype 786 T/T was significantly
more increased in the two disease groups than controls X2 and P-value of (7.2, 0.0002) in
T2DM group and (18.11, 0.0001) in CAD plus T2DM group respectively. Bioinformatics
analysis was carried out for 894 G/T polymorphism by modeling and comparing normal vs.
mutant protein. Significant differences were observed in the parameters of two models,
indicating the effect of 894 G/T polymorphism on protein structure and hence function. Thus, it can be concluded that 786 T/C polymorphism in the promoter region is significantly associated with T2DM and CAD in Pakistani patients.
