Rs7574865 polymorphism of STAT4 and risk of anti-tuberculosis drug-induced hepatotoxicity in Chinese Han

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is the most frequent, and potentially fatal adverse effect in the treatment of tuberculosis (TB). The rs7574865 polymorphism in the signal transducer and activator of transcription 4 gene ( STAT4 ) was reported to be associated with drug-induced liver injury. However, there was no study aimed to this association in Chinese patients. The aim of this study was to investigate the influence of STAT4 polymorphisms on the susceptibility to ATDH in a Chinese Han population. A total of 280 TB patients with the prescription of anti-TB therapy, of Chinese Han origin, were enrolled. They were followed up for 3 months and demographic, clinical, laboratory and therapeutic data at each visit were collected. Two single nucleotide polymorphisms (SNPs) (rs7574865 and rs7582694) of STAT4 were genotyped with the MassARRAY platform. The associations between SNPs and ATDH risk were analyzed by logistic regression adjusting for confounding factors. A total of 24 patients were diagnosed with ATDH and considered as the case group, and 33 patients were lost to follow-up; the remaining 223 subjects without ATDH were considered as the control group. There was strong linkage disequilibrium (LD) between rs7574865 and rs7582694 (r 2 = 0.928 and D′ = 1). No significant association was found between SNPs or haplotypes of STAT4 and ATDH after correction for confounding factors. This prospective study is the first to investigate the association of genetic polymorphisms of STAT4 and ATDH in Chinese individuals. There was no significant association between the rs7574865 of STAT4 and ATDH in a Chinese Han population.