TNF-α genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis

Background: While the mechanisms underlying the development of druginduced liver injury are not clear, there is evidence to suggest that tumor necrosis factor-a (TNF-a) plays an important role in drug-or drug metabolite- induced immune responses. We hypothesized that polymorphisms in the TNF-a gene are associated with anti-tuberculosis drug (ATD)-induced hepatitis. Methods: Patients who suffered from ATD-induced hepatitis were enrolled in the study. ATD-induced hepatitis was defined as an increase in liver transaminase levels that were more than three times the upper limit of normal. ATD-tolerant patients were used as a control. Patients were treated with first line ATD therapies including isoniazid, rifampicin, ethambutol, and pyrazinamide. We compared the genotype frequencies of the TNF-a polymorphism -308G/ A in 77 patients with ATD-induced hepatitis and 229 ATD-tolerant patients. Results: The frequency of carrying the variant allele (AG or AA) was significantly higher in patients with ATD-induced hepatitis compared with ATD-tolerant patients [26.0% vs. 15.3%, P = 0.034, OR (95% CI) = 1.94 (1.04-3.64)] and the frequency of the A allele was significantly different between the two groups [0.143 vs. 0.079, P = 0.018, OR (95% CI) = 1.95 (1.11-3.44)]. Conclusion: These results reveal that the TNF-a genetic polymorphism -308G/ A is significantly associated with ATD-induced hepatitis. This genetic variant may be a risk factor for ATD-induced hepatitis in individuals from Korea.