Association of Nat2 Gene Polymorphism with Antitubercular Drug-induced Hepatotoxicity in the Eastern Uttar Pradesh Population

摘要

Introduction Tuberculosis (TB) remains an important cause of morbidity and mortality?worldwide. There are more than 20 drugs available for TB treatment. Hepatotoxicity is the most serious adverse drug reaction of anti-TB drugs. Various pathogenesis and genetic factors are associated with antituberculosis drug-induced hepatotoxicity (ATDIH). Antituberculosis drugs (ATDs) are mostly metabolized by N-acetyltransferase 2 (NAT2). Therefore, in this study, we aim to evaluate the role of the NAT2 genotype in ATDIH in the eastern Uttar Pradesh population. Methods A total?of 100?TB patients who had been treated with anti-TB drugs were enrolled in this studied. In this group, 70 TB patients did not develop drug-induced hepatotoxicity (tolerant control group) and 30 TB patients developed ATDIH (ATDIH group). The genetic polymorphisms of the NAT2 genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype and allele frequencies were evaluated by the t-test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results There is a?high percentage of slow acetylators in the Eastern Uttar Pradesh population. Four percent?of people?are fast acetylators, 34% are intermediate acetylators, and 62% are slow acetylators. The?frequency of slow acetylators in the NAT2 genotype was commonly present and was not significantly different between the ATDIH (73.33%) and tolerant control groups (61.40%). However, the genotypic distribution of variants of slow-acetylator genotypes (NAT2*6/7, NAT2*5/7,?and NAT2*5/6) was also not significantly different in ATDIH. Conclusion In the?present study, the slow acetylators of the NAT2 genotype did not contribute to the elevated risk of ATDIH development in tuberculosis patients.