The distribution of N-acetyltransferase 2 genotypes in a cohort of tuberculosis patients in a single center in Henan Province of China

Background Genetic variation in N-acetyltransferase 2 (NAT2) affects isoniazid metabolism, but acetylator distributions and their association with liver abnormalities remain incompletely characterized in central China. We described genotype-inferred NAT2 acetylator status and assessed its association with new in-hospital liver function abnormality among patients with tuberculosis. Methods This retrospective, single-center study included 801 patients who underwent NAT2 genotyping at Henan Provincial Chest Hospital between January 2021 and May 2024. The overall cohort was used to describe slow (SA), intermediate (IA), and fast (FA) acetylator distributions. The primary analysis included 554 patients with normal liver function at admission and a recorded isoniazid dose; 690 patients with normal baseline liver function formed the secondary cohort. The primary comparison was SA versus non-SA. Logistic regression adjusted for age, sex, and recorded isoniazid dose, with additional and sensitivity analyses. Results Among 801 patients, 369 (46.1%) were IA, 278 (34.7%) were FA, and 154 (19.2%) were SA. In the primary analysis, 143 patients developed a new in-hospital liver function abnormality. The event rate was 28.7% (29/101) in SA and 25.2% (114/453) in non-SA (crude odds ratio [OR], 1.20; 95% confidence interval [CI], 0.73–1.92; P = 0.462). After adjustment for age, sex, and recorded isoniazid dose, SA was not significantly associated with the outcome (adjusted OR, 1.18; 95% CI, 0.72–1.89; P = 0.507). Additional adjustment for pulmonary tuberculosis and isoniazid susceptibility produced the same estimate (OR, 1.18; 95% CI, 0.72–1.90; P = 0.505). Secondary and sensitivity analyses were consistent. At 80% power, the approximate minimum detectable OR for a risk-increasing association was 1.94. Conclusions Slow acetylator status was not significantly associated with new in-hospital liver function abnormality, although smaller or moderate effects could not be excluded. Because the outcome was not causally adjudicated ATB-DILI and systematic pharmacokinetic and longitudinal treatment data were unavailable, these findings do not establish the clinical utility of NAT2-guided dosing. Prospective multicenter validation is needed.