Study of TNF-α Polymorphism (308G/A) and the Role of NF-κB as an Novel Marker of Severity of Atherosclerosis: A Pilot Study in Indian Population

Background: Biallelic polymorphism of A/G variation at position 308 in the promoter region of TNF-α gene is an important genetic factor causing high TNF-α transcription which could influence the clinical outcome of atherosclerosis. Studies have also implicated the role of NF-κB in atherogenesis by regulating genes involved in the inflammatory response and insulin sensitivity. Material and Method: 50 cases of angiographically significant atherosclerosis (>50% obstruction in coronary arteries) and 50 age, sex, BMI matched patients with insignificant atherosclerosis (>50% obstruction) on angiography were selected from GB Pant Hospital. Polymorphism was studied by amplifying DNA using PCR and amplified segments were digested by restriction enzyme Nco-I and followed by RFLP. Serum NF-κB, TNF-α levels were estimated by sandwich ELISA. Results: The mean serum NF-κB and TNF-α levels were significantly (p=0.04, 0.000 respectively) raised in cases as compared to controls. Upon binomial logistic regression analysis, NF-κB emerged as the best predictor of severity of atherosclerosis (Odds ratio=27) among other markers. Our results showed no intergenotypic variation of 308-G/A polymorphism of the TNF-α gene between cases and controls. Conclusion: Our study establishes NF-κB as an emerging biomarker of severity of atherosclerosis in Indian population. No intergenotypic variation between cases and controls indicates that significantly high levels of TNF-α in the cases is attributed to cause other than polymorphism in Indian population. High prevalence of chronic low grade inflammation in population could be postulated as the possible cause.