Influence of N-acetyltransferase 2 polymorphisms and clinical variables on liver function profile of tuberculosis patients.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Expert Review of Clinical Pharmacology Pub Date : 2024-03-01 Epub Date: 2024-02-01 DOI:10.1080/17512433.2024.2311314

Levin Thomas, Arun Prasath Raju, S Chaithra, Shrivathsa Kulavalli, Muralidhar Varma, Chidananda Sanju Sv, Mithu Baneerjee, Kavitha Saravu, Surulivelrajan Mallayasamy, Mahadev Rao

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Abstract

Background: Single nucleotide polymorphisms (SNPs) in the N-acetyltransferase 2 (NAT2) gene as well as several other clinical factors can contribute to the elevation of liver function test values in tuberculosis (TB) patients receiving antitubercular therapy (ATT).

Research design and methods: A prospective study involving dynamic monitoring of the liver function tests among 130 TB patients from baseline to 98 days post ATT initiation was undertaken to assess the influence of pharmacogenomic and clinical variables on the elevation of liver function test values. Genomic DNA was extracted from serum samples for the assessment of NAT2 SNPs. Further, within this study population, we conducted a case control study to identify the odds of developing ATT-induced drug-induced liver injury (DILI) based on NAT2 SNPs, genotype and phenotype, and clinical variables.

Results: NAT2 slow acetylators had higher mean [90%CI] liver function test values for 8-28 days post ATT and higher odds of developing DILI (OR: 2.73, 90%CI: 1.05-7.09) than intermediate acetylators/rapid acetylators.

Conclusion: The current study findings provide evidence for closer monitoring among TB patients with specific NAT2 SNPs, genotype and phenotype, and clinical variables, particularly between the period of more than a week to one-month post ATT initiation for better treatment outcomes.

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N- 乙酰转移酶 2 多态性和临床变量对肺结核患者肝功能状况的影响

背景：N-乙酰转移酶2（NAT2）基因中的单核苷酸多态性（SNPs）以及其他一些临床因素可能会导致接受抗结核治疗（ATT）的肺结核（TB）患者肝功能检测值升高：这项前瞻性研究对 130 名肺结核患者从基线到 ATT 开始后 98 天的肝功能检测进行了动态监测，以评估药物基因组学和临床变量对肝功能检测值升高的影响。为评估 NAT2 SNPs，我们从血清样本中提取了基因组 DNA。此外，我们还在该研究人群中开展了一项病例对照研究，根据 NAT2 SNPs、基因型和表型以及临床变量来确定 ATT 引起的药物性肝损伤（DILI）的发病几率：结果：NAT2缓慢乙酰化者在ATT后8-28天的肝功能检测平均值[90%CI]比中等乙酰化者/快速乙酰化者高，发生DILI的几率也更高（OR：2.73，90%CI：1.05-7.09）：目前的研究结果为密切监测结核病患者的特定 NAT2 SNPs、基因型和表型以及临床变量提供了证据，尤其是在 ATT 开始后一周以上至一个月期间，以获得更好的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.30

自引率

2.30%

发文量

127

期刊介绍： Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.