title: TNF-α genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis.
abstract: 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 (1.043.64)] 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 (1.113.44)].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho Joo
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Shin
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Park
authors.forename: Youn-Seup
authors.initials: YS
authors.lastname: Kim
authors.forename: Jae-Seuk
authors.initials: JS
authors.lastname: Park
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D014409:Tumor Necrosis Factor-alpha