Effects of FECH Gene Polymorphisms and Serum Ferrochelatase Levels on Antituberculosis Drug-Induced Liver Injury in China.

OBJECTIVES

The pathogenic mechanism of antituberculosis drug-induced liver injury (ATLI) has not been elucidated. This study aimed to investigate the effects of FECH genetic polymorphisms and serum ferrochelatase levels on ATLI in the Chinese population.

METHODS

One case-control study was conducted to investigate the association between four SNPs in FECH gene and ATLI, while another was used to analyze the association of serum ferrochelatase levels at three different times with ATLI. Multivariate logistic regression model was used to screen potential risk factors for ATLI, and the results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The area under receiver operating characteristic curve (AUC) was calculated to estimate the performance for distinguishing ATLI cases from controls.

RESULTS

Serum ferrochelatase levels were lower in ATLI cases than in controls at the time of baseline test, the first test and the second test after initial treatment. A multivariate logistic regression model showed that SNP rs536560 in the FECH gene (OR = 2.063, 95%CI: 1.112-3.892, p = 0.023), baseline serum ferrochelatase level (OR = 3.162, 95%CI: 1.605-6.234, p = 0.001), and liver disease history (OR = 2.915, 95%CI: 1.301-6.461, p = 0.008) were the risk factors for ATLI. The ROC curves demonstrated that the model including the above three factors has strong discriminating ability (AUC = 0.709, 95%CI: 0.639-0.779, p < 0.0001).

CONCLUSIONS

This study is the first to explore the relationships between SNPs in the FECH gene, serum ferrochelatase levels, and ATLI in China, and SNP rs536560 in the FECH gene, baseline ferrochelatase level, and liver disease history may be associated with susceptibility to ATLI.