DM is one of the five principal causes of death universally. It is a growing heath problem of 
multifactorial origin, understanding its genetic background might help in early detection and disease 
prevention. Obesity, especially visceral adiposity, and physical inactivity are major risk factors for 
diabetes in Egypt. A 2010 World Health Organization (WHO) report indicated that 30.3% of 
Egyptian adults are obese. Egypt currently has the third highest prevalence of obesity in the Middle 
East and North Africa (MENA) region, after Saudi Arabia and United Arab Emirates. It has been 
reported that genetic variations in the promoter region regulate tumor necrosis factor-α (TNFα) 
production and transcription and, they influence susceptibility to inflammatory related diseases. 
Single nucleotide polymorphism studies in the promoter region of TNFα (_238) have suggested its 
role in increased insulin resistance. This is a prospective case control study aimed at detecting the 
impact of TNF α 238 G/A rs 361525 gene polymorphisms in T2DM in Egyptian population. It 
included 40 diabetic patients, and 40 apparently healthy unrelated volunteers. We underwent history 
taking, clinical examination with detection of BMI and W/H ratio, laboratory investigations, (finger 
prick test, 75 gram oral glucose tolerance test, HA1C, fasting and 2hPP blood glucose, and detection 
of TNF -238G/A gene polymorphisms that was performed by using PCR/RFLP method. In respect to 
the distribution of TNFα 238 G/A polymorphism genotypes: In patients with T2DM it was (GG 
genotype: 75%, AA genotype 5%, and GA genotype: 20%). In control it was (GG genotype: 90%, 
AA genotype: 2.5%, and GA genotype: 7.5%).