Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Departamento de Fármacos e Medicamentos, Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro, Faculdade de Farmácia, Departamento de Fármacos e Medicamentos, Rio de Janeiro, RJ, Brazil.
Braz J Infect Dis. 2019 Nov-Dec;23(6):381-387. doi: 10.1016/j.bjid.2019.09.003. Epub 2019 Nov 4.
Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH). DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH.
To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers.
This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used.
The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses.
Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p=0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.
抗结核治疗（TB）可能导致药物性肝损伤（DILI），因为异烟肼（INH）在生物转化过程中会形成肝毒性代谢物。DILI 可能与患者的遗传特征有关。CYP2E1 基因中的单核苷酸多态性以及 GSTM1 和 GSTT1 缺失多态性与 INH 引起的不良事件有关。
描述携带结核分枝杆菌患者 CYP2E1、GSTM1 和 GSTT1 的遗传多态性。
这是一项观察性前瞻性队列研究，共纳入 45 名正在接受 TB 治疗的患者。使用 PCR-RFLP 和多重 PCR 进行分析。
启动子区域（CYP2E1 基因）的基因型频率分布为：98%野生型，2%杂合型。内含子区域：78%野生型；20%杂合型，2%纯合型变异。GST 酶基因：24%的 GSTM1 缺失型和 22%的 GSTT1 缺失型。在统计分析中，将 CYP2E1 基因存在任何变异等位基因的患者归为一组。
携带 CYP2E1 变异基因型或 GSTT1 缺失型的患者发生 DILI 的风险更高（p=0.09；OR：4.57；95%CI：0.75-27.6）。与携带一种基因型的个体相比，同时携带两种基因型的个体没有增加风险。
