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TNF ‐α genetic polymorphism −308G/A and antituberculosis drug‐induced hepatitis
Author(s) -
Kim SangHeon,
Kim SangHoon,
Yoon Ho Joo,
Shin Dong Ho,
Park Sung Soo,
Kim YounSeup,
Park JaeSeuk,
Jee YoungKoo
Publication year - 2012
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02697.x
Subject(s) - pyrazinamide , medicine , hepatitis , ethambutol , isoniazid , genotype , immunology , liver injury , allele , tumor necrosis factor alpha , rifampicin , hepatitis c , drug , allele frequency , tuberculosis , gastroenterology , pharmacology , pathology , gene , biology , biochemistry
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)]. 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.