Sahiratmadja Edhyana, Rini Ika Agus, Penggoam Simeon, Charles Afandi, Maskoen Ani Melani, Parwati Ida
Division of Biochemistry and Molecular Biology, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
Health Research Unit, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
Pharmgenomics Pers Med. 2021 Jun 22;14:737-744. doi: 10.2147/PGPM.S311952. eCollection 2021.
N-acetyltransferase-2 enzyme in the liver, encoded by gene, plays a central role in metabolizing tuberculosis (TB) drug isoniazid (INH). Low compliance of patients toward six-month TB therapy and internal host factors, ie comorbid diseases, immune status, and genetic profiles, are factors leading to treatment failure and recurrence of pulmonary TB infection. This study aimed to explore the NAT2 acetylator status among newly diagnosed and recurrent pulmonary TB patients in eastern part of Indonesia.
Archived DNA of TB patients (n=124) and healthy controls (n=124) were sequenced, and acetylator status was determined, then categorized as fast, intermediate, or slow acetylators. Pulmonary TB patients who had no previous TB treatment history were designated as newly diagnosed pulmonary TB, whereas patients with a history of TB treatment were designated as recurrent pulmonary TB. The demographic, clinical, and microbiological data between pulmonary TB groups were compared, and acetylator status was described among groups.
Male was more significantly prevalent in the recurrent pulmonary TB group (p=0.025), and anemia was more prevalent in new pulmonary TB (p=0.003). The acetylator status in pulmonary TB patients compared to healthy controls were rapid (33.9% vs 48.1%), intermediate (57.8% vs 33.0%), and slow acetylators (8.3% vs 18.9%), respectively. Interestingly, the rapid and intermediate acetylator were significantly more prevalent in pulmonary TB patients than in healthy controls (p=0.023, OR=2.58 (1.12-5.97). Furthermore, no differences were found in acetylator status between new and recurrent pulmonary (p=0.776).
Rapid and intermediate acetylators status predominated the pulmonary TB patients in Kupang, eastern part of Indonesia, postulating different genetic makeup in this area. As the pulmonary TB patients in Kupang exhibit more rapid acetylator phenotype, the acetylator status might be relevant to be checked before TB therapy for adjusting treatment dose to prevent drug resistances.
由基因编码的肝脏中的N - 乙酰转移酶 - 2酶在代谢结核病(TB)药物异烟肼(INH)中起核心作用。患者对六个月结核病治疗的低依从性以及宿主内部因素,即合并症、免疫状态和基因谱,是导致治疗失败和肺结核感染复发的因素。本研究旨在探讨印度尼西亚东部新诊断和复发性肺结核患者中的NAT2乙酰化状态。
对结核病患者(n = 124)和健康对照者(n = 124)的存档DNA进行测序,确定乙酰化状态,然后分为快速、中间或慢速乙酰化者。既往无结核病治疗史的肺结核患者被指定为新诊断的肺结核患者,而有结核病治疗史的患者被指定为复发性肺结核患者。比较肺结核组之间的人口统计学、临床和微生物学数据,并描述各组的乙酰化状态。
复发性肺结核组男性更为显著地普遍存在(p = 0.025),新诊断的肺结核患者中贫血更为普遍(p = 0.003)。与健康对照相比,肺结核患者中的乙酰化状态分别为快速(33.9%对48.1%)、中间(57.8%对33.0%)和慢速乙酰化者(8.3%对18.9%)。有趣的是,快速和中间乙酰化者在肺结核患者中比在健康对照中更为显著地普遍存在(p = 0.023,OR = 2.58(1.12 - 5.97))。此外,新诊断和复发性肺结核患者之间的乙酰化状态没有差异(p = 0.776)。
快速和中间乙酰化状态在印度尼西亚东部古邦的肺结核患者中占主导地位,推测该地区存在不同的基因构成。由于古邦的肺结核患者表现出更多的快速乙酰化者表型,在结核病治疗前检查乙酰化状态可能与调整治疗剂量以预防耐药性相关。