Relevance of NAT2 genotype to anti‐tuberculosis drug‐induced hepatotoxicity in a Chinese Han population

Abstract

Background Anti‐tuberculosis drug‐induced hepatotoxicity (ATDH) is a serious adverse drug reaction. The slow acetylator status of N‐acetyl transferase 2 (NAT2) is a well‐established risk factor for ATDH. One novel tagging single nucleotide polymorphism (tagging SNP), rs1495741, in NAT2 has been found to be highly predictive of the NAT2 phenotype. The present study aimed to validate the relationships between tagging SNP rs1495741 and ATDH in a Chinese Han population. Methods A 1:2 matched case–control study was conducted using 235 ATDH cases and 470 controls. Conditional or unconditional logistic regression analysis was used to estimate the association between genotypes and the risk of ATDH according to the odds ratio (OR) with a 95% confidence interval (CI). Results Patients carrying the AA genotype of tagging SNP rs1495741 were at higher risk of ATDH than those carrying the GG genotype (OR = 1.653, 95% CI = 1.050–2.601; p = 0.030). Subgroup analysis suggested that the AA genotype was a risk factor for ATDH in patients aged older than 50 years (OR = 2.486, 95% CI = 1.313–4.706; p = 0.005), weighing over 50 kg (OR = 1.757, 95% CI = 1.016–3.038; p = 0.044) or using a hepatoprotectant (OR = 1.611, 95% CI = 1.009–2.572; p = 0.046). Tagging SNP rs1495741 was not a significant risk factor for moderate and severe hepatotoxicity but appears to be relevant to risk of mild hepatotoxicity specifically. Conclusions The present study is the first to validate the relationships between the tagging SNP rs1495741 and ATDH in a Chinese population. Based on this case–control study, the NAT2 rs1495741 polymorphism is a risk factor for mild but not more severe ATDH in Chinese Han patients.