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

Sang Heon Kim, Sang Hoon Kim, Ho Joo Yoon, Dong Ho Shin, Sung Soo Park, Youn Seup Kim, Jae Seuk Park, Young Koo Jee

Research output: Contribution to journalArticle

16 Citations (Scopus)

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)]. 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.

Original languageEnglish
Pages (from-to)809-814
Number of pages6
JournalLiver International
Volume32
Issue number5
DOIs
StatePublished - 2012 May 1

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Chemical and Drug Induced Liver Injury
Genetic Polymorphisms
Tuberculosis
Tumor Necrosis Factor-alpha
Pharmaceutical Preparations
Pyrazinamide
Ethambutol
Isoniazid
Rifampin
Korea
Transaminases
Gene Frequency
Alleles
Genotype

Keywords

  • Antituberculosis drugs
  • Genetic polymorphism
  • Hepatitis
  • Tumour necrosis factor-α

Cite this

Kim, Sang Heon ; Kim, Sang Hoon ; Yoon, Ho Joo ; Shin, Dong Ho ; Park, Sung Soo ; Kim, Youn Seup ; Park, Jae Seuk ; Jee, Young Koo. / TNF-α genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis. In: Liver International. 2012 ; Vol. 32, No. 5. pp. 809-814.
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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)]. 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.",
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TNF-α genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis. / Kim, Sang Heon; Kim, Sang Hoon; Yoon, Ho Joo; Shin, Dong Ho; Park, Sung Soo; Kim, Youn Seup; Park, Jae Seuk; Jee, Young Koo.

In: Liver International, Vol. 32, No. 5, 01.05.2012, p. 809-814.

Research output: Contribution to journalArticle

TY - JOUR

T1 - TNF-α genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis

AU - Kim, Sang Heon

AU - Kim, Sang Hoon

AU - Yoon, Ho Joo

AU - Shin, Dong Ho

AU - Park, Sung Soo

AU - Kim, Youn Seup

AU - Park, Jae Seuk

AU - Jee, Young Koo

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

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KW - Genetic polymorphism

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