IS there a relation between TNF-α 308 Promoter Gene Polymorphism and a risk of Coronary Artery Disease In patients with Type 2 Diabetes Mellitus?

The hypothesis that both atherosclerosis and type 2 diabetes mellitus share the common antecedent of chronic inflammatory disorders has been gaining acceptance. In fact, abnormalities in immune system function and inflammatory mediators have been found to be associated with several classic cardiovascular risk factors such as hypertension, dyslipidemia, endothelial dysfunction, clotting activation and insulin resistance. one of the most important factors that promote inflammation and arterial thrombosis, is the proinflammatory cytokine TNF-alpha. The expression of this cytokine is modulated by a polymorphism located at nucleotide -308 of the TNF-alpha promoter gene. Objective: In this study we investigated the impact of the G-308A TNF-alpha polymorphism on the development of CAD in type 2 diabetes mellitus patients. Subjects and Methods: We studied 40 subjects, who were categorized into 3 groups, 15 patients having DM type 2 with CAD as group (I), 15 patients having DM type 2 without CAD as (group II), and 10 apparently healthy volunteers served as control group (group III). all patients and controls were subjected to the followings: complete history taking, clinical evaluation, routine laboratory investigations and detection of TNF alpha gene (-308) polymorphism by restriction fragment length polymorphism (RFLP). AA and GA genotypes of TNF-alpha 308 were significantly increase in group I (DM2 with CAD) when compared to group II (DM2 without CAD) and control group, while there was significant decrease in GG genotype in group I when compared to group II and control group. Additionally, there were significant increase of FBG, 2H.P.P blood glucose, T. Cholesterol, LDL and Serum Triglyceride levels in mutant genotypes (AA + GA) when compared to wild genotype (GG), while there was significant decrease of HDL level in mutant genotypes when compared to wild genotype. In conclusion, our study indicates that the TNF-a 308G/A polymorphism may be a potent risk factor for coronary artery disease and associated risk of metabolic diseases in diabetic patients.