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

Background: While the mechanisms underlying the development of drug-induced liver injury are not clear, there is evidence to suggest that tumor necrosis factor-α (TNF-α) plays an important role in drug- or drug metabolite-induced immune responses. We hypothesized that polymorphisms in the TNF-α 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-α 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-α 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.