[Association of P450-2E1 and GSTM1 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity].

OBJECTIVE: To observe the relationship between the genetic polymorphism of P450-2E1 and the risk for antituberculosis drug-induced hepatotoxicity in a Chinese population.

METHODS: Blood samples and clinical data were collected from 85 patients with antituberculosis drug-induced hepatotoxicity and 100 tuberculosis patients without hepatotoxicity as the control. DNA was extracted from the blood samples, and the frequencies of P450-2E1 RsaI genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the polymorphisms of P450-2E1 RsaI and the antituberculosis drug-induced hepatotoxicity was analyzed. Predisposing factors for antituberculosis drug-induced hepatitis, such as gender, age, and polymorphism of P450-2E1 RsaI were evaluated by using logistic regression analysis.

RESULTS: The frequencies of the 3 gene types P450-2E1 RsaI c1/c1, c1/c2, and c2/c2 were 75% (64/85), 20% (17/85) and 5% (4/85) respectively in patients with antituberculosis drug-induced hepatotoxicity, and 61% (61/100), 30% (30/100), and 9% (9/100) respectively in the controls. A statistical difference was found between the cases and the controls (chi(2) = 4.284, P < 0.05, OR = 2.016, 95%CI = 1.058 - 3.842). Logistic regression analysis showed that the polymorphism of P450-2E1 RsaI remained a significant independent risk factor for antituberculosis drug-induced hepatotoxicity after adjustment for age, gender and body mass index.

CONCLUSION: Polymorphisms of P450-2E1 were found to be significantly associated with the risk of antituberculosis drug-induced hepatotoxicity, and the c1/c1 genotype was one of the risk factors.