The Variant at TGFBRAP1 but Not TGFBR2 Is Associated with Antituberculosis Drug-Induced Liver Injury

Abstract

Background. TGFBRAP1 and TGFBR2 play important roles in the TGF-β/smad signalling pathway and may disturb liver homeostasis by regulating liver injury and renewal. However, little is known about the association between their genetic polymorphisms and antituberculosis drug-induced liver injury (ATDILI), so we explored the association between their variants and the susceptibility to ATDILI. Materials and Methods. A total of 746 tuberculosis patients were prospectively enrolled, and fifteen selected SNPs were genotyped. The allele, genotype, and genetic model frequencies of the variants were compared between patients with or without ATDILI, as well as the joint effect analysis of SNP-SNP interactions. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated. Results. The A variant at rs17687727 was significantly associated with an increased risk for ATDILI (OR 1.55; 95% CI: 1.08–2.22; p=0.016), which is consistent with the results in the additive and dominant models. Other allele, genotype, and genetic model frequencies were similar in the two groups for the other fourteen SNPs (all p>0.05). Conclusion. Our study first implied that the A variant of rs17687727 in TGFBRAP1 influenced the susceptibility to ATDILI in first-line antituberculosis combination treatment in the Han Chinese population in a dependent manner.