TNF - α Gene Polymorphism is Likely to be a Risk Factor for NASH in Indonesia

Introduction : Non alcoholic steatohepatitis (NASH) is a subset spectrum of NAFLD that can progress toward cirrhosis. Tumor necrosis factor- α (TNF- α) polymorphism play a significant role in liver inflammation and Insulin resistance its pathophysiological hallmark. The association between TNF- α (-238 and -308) polymorphism) and the severity of NAFLD was evaluated. Method: A total of 155 subjects (80 NAFLD cases and 75 controls) were included. Liver biopsy was performed for evaluated severity of NAFLD based on NAFLD Activity Score-CRN in all cases. Controls subjects defined was not any liver disease by ultrasound. Plasma TNF– α was measured in all subjects. Polymorphism of` TNF- α promoter gene -308 and -238 were identified using PCR-RFLP confirmed with direct sequencing. Results: Liver biopsy established the diagnosis of NASH in 29 cases. There was no association between the incidence of NAFLD with TNF- α polymorphism at the TNF– α -308 or the -238 (p>0.05). The prevalence ratio of TNF– α polymorphism -238 was significantly higher for subject with NASH (p< 0.02). There was no different prevalence ratio for TNF– α polymorphism -308 (p>0,05). We found novel polymorphism of TNF- α -245 T/C in a subject with possible NASH, high plasma TNF- α level (20.27 pg/cc) and very high value of Homeostasis Model of Assessment - Insulin Resistance HOMA-IR (22.73). Conclusion : Polymorphism TNF- α -238 is likely to be a risk factor for NASH in Indonesia. The identification of new possible polymorphism of TNF- α -245 requires further study in more samples.