Do genetic polymorphisms of B-cell CLL/lymphoma 2 confer susceptibility to anti-tuberculous therapy-associated drug-induced liver injury?

摘要

Objectives The aim of this study was to identify the relationship between B-cell CLL/lymphoma 2 ( BCL2 ) polymorphisms and susceptibility to anti-tuberculous therapy-associated drug-induced liver injury (ATT-DILI). Methods A total of 746 tuberculosis (TB) patients were enrolled in this study. Twenty-one selected single nucleotide polymorphisms in BCL2 were analyzed by custom-by-design 2?×?48-Plex SNPscan kit. The allele and genotype frequencies between patients with and without ATT-DILI were compared using three different genetic models. Results A total of 727/746 participants were successfully genotyped, and 112 of them were diagnosed with ATT-DILI. The A allele of rs8085707, G allele of rs76986960, and A allele of rs949037 conferred an increased risk of ATT-DILI, with estimated odd ratios (ORs) of 2.181 (95% confidence interval (CI) 1.345–3.536, p ?=?0.001), 1.983 (95% CI 1.060–3.709, p ?=?0.029), and 1.390 (95% CI 1.032–1.873, p ?=?0.03), respectively. Bonferroni correction indicated that the A allele of rs8085707 was a risk factor for ATT-DILI (Bonferroni correction: p ?=?0.026). The additive model suggested that patients with the AA genotype of rs8085707 had a significantly higher risk of ATT-DILI compared with those with the GG genotype (Bonferroni correction: p ?=?0.036). The influence of BCL2 polymorphisms on clinical characteristics (clinical symptoms, disease subtypes, and laboratory indicators) was also identified. Conclusions This study is novel in suggesting an association between BCL2 polymorphisms and the risk of ATT-DILI.