NAT2 Involed in the Susceptibility to Antituberculosis Drug-Induced Liver Injury

• 作者: Changzhi Xu Donglin Zhu Gang Xiao Yun Xi Zhizhi Xie
• 来源期刊: 医学科学进展杂志(英文)
• 学科: 医学
• 关键词: NAT2 MassARRAY TUBERCULOSIS Liver injury GENETIC POLYMORPHISM
• 年，卷（期）: 2019,（3）
• 页码范围: 6-11
• 页数: 6页
• 分类号: R

摘要

Objective: To investigate whether the N-acetyltransferase 2 (NAT2) gene is involved in the development of susceptibility to antituberculosis drug-induced liver damage (ATDLI) in patients with pulmonary tuberculosis in the Han nationality. Methods: We retrospectively analyzed 300 cases of tuberculosis patients without liver damage (control group) and 221 cases of tuberculosis patients with liver damage after antituberculosis treatment (case group). After antituberculosis treatment, genetic polymorphisms of NAT2 were analyzed in those patients using MassARRAY method. Results: Of the 10 tagged SNPs selected, In the promoter area of NAT2, the frequencies of T allele in rs4646243 and A allele in rs4646246 were significantly higher in the patients with ATDLI than controls (0.569 vs. 0.483, p=0.0062 and 0.567 vs 0.487, p=0.0103). The A allele of rs1115784 in the intron area showed a significant association with the development of ATDLI (0.389 vs 0.305, p = 0.0043). The frequencies of the mutated genes T and A in rs1041983 and rs1799930 in the second exon region were significantly higher than those in the control group (0.491 vs 0.360, p<0.00001 and 0.336 vs 0.212, respectively;p<0.00001). Two monomer domains were found in the 10 tag SNP sites, haplotype ht [TGAA] in monomeric domain 1 and haplotype ht [TAG] in monomeric domain 2, both were significantly more likely to be detected in the liver injury group than in the control group(p=0.0038, p<0.001, respectively). Two haplotypes were also found on the NAT2 gene: haplotype ht [CGGG] in monomeric domain 1 and ht [CGG] in block 2, and their presence means a lower risk of liver damage. Conclusion: NAT2 genotypes might have significant association with the risk of ATDLI in the Chinese Han nationality. By detecting the NAT2 gene and its haplotype, we can screen patients with a higher risk of liver damage before anti-TB treatment and take measures for the protection of patients.