Single nucleotide polymorphism (SNP) studies in the promoter region of tumor necrosis factor-alpha (TNF-α (238)) have suggested its role in increased insulin resistance and also in the progression from prediabetes to type 2 diabetes (T2DM). It has been reported that genetic variations in the promoter region regulate TNF-α production and transcription, and they influence susceptibility to inflammatory-related diseases. Impairment of normal functioning of the β-cells of pancreatic islets is one of the main causative factors for the suppression of insulin secretion. TNF-α is among the main stimuli that induce the inflammation in pancreatic islets which lead to the induction of apoptosis in β-cells of pancreatic islets. Transcription factor 7-like 2 (TCF7L2) gene has been found to be one of the most risky genes for prediabetes and progression toT2DM. However, the underlying mechanism of this is still unknown. This is a review article demonstrating the possible mechanisms of both TNF-α G/A 238 and TCF7L2 C/T gene polymorphisms in prediabetes and type 2 diabetes mellitus.

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%).