TNF-A GENE (308G/A) PROMOTER REGION POLYMORPHISM IN METABOLIC SYNDROME: A PILOT STUDY IN NORTH INDIA.

Introduction: Metabolic Syndrome is attracting a lot of scientific and commercial interest as the factors defining the syndrome are all associated with increased morbidity and mortality in general and there is still lot of controversy in definitions as well as pathophysiology due to multifactorial etiology. Inflammation and genetic factors play important role along with other factors. Aim: To study the association of TNF-α gene (308G/A) promoter region polymorphism with metabolic syndrome and to study inter genotypic variation of TNF α levels in cases and controls. Materials and Methods: A total of 93 subjects (46 Cases & 47 Controls) were enrolled into the study with informed consent. All subjects were above 25 years of age & cases had metabolic syndrome diagnosed according to IDF 2006 criteria (for Asian population) while controls were age- and sex-matched healthy subjects not fitting into IDF 2006 criteria. TNF-α levels were estimated by Sandwich ELISA and promoter region polymorphism was studied by DNA extraction followed by Polymerase Chain Reaction and Restriction fragment Length Polymorphism. Results: TNF-α level among cases (16.48?6.68 pg/mL) was significantly higher than controls (1.90?0.80 pg/mL). In cases, GG genotype was found in 63 % (29); GA in 33% (15), followed by AA in 4% (2). Among controls GG genotype was present in 85% (40) and GA in 15% (7) and no subject had AA genotype. The genotype distribution was in Hardy Weinberg Equilibrium (χ2 = 6.653, df = 2, p < 0.05). The difference was found statistically significant (p < 0.001). Allelic Frequency difference between the two groups was also significant (p < 0.05). Intergenotypic variations in the levels of TNF-α came significantly different (p<0.05) by ANOVA and T Test Conclusion: We conclude that inflammation is involved in etiopathogenesis of MetS and GA and AA genotype is associated with increased transcription of TNF-α suggesting their regulation at genetic level.