Genetic Tests may Help Improve Patients’ Response to Tuberculosis Medication
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Experts have highlighted the role that genetics may play in treating the current global tuberculosis (TB) pandemic. Paul van Helden and colleagues, from Stellenbosch University in South Africa, outlined the role that different genetic mutations may play in determining how a patient will respond to the commonly used TB medication isoniazid. These observations are published in the May issue of the journal Personalized Medicine.
It is estimated that at least 8 million people develop active TB annually, of whom 2 million die. It has been the cause of a global health emergency for over 10 years owing to factors such as social stigma, patient compliance and lack of investment in a thorough TB control program.
Recently, these factors have resulted in the worrying emergence of drug resistance, leading to multi-drug resistant (MDR) and extensively drug resistant (XDR) strains of TB becoming prevalent. This is a particular problem in the developing world, where the majority of patients with TB also have HIV, making effective eradication extremely difficult.
Isoniazid is a commonly used and relatively inexpensive first-line TB drug. It is metabolized in the liver at different speeds in different individuals, giving rise to ‘fast, intermediate and slow acetylator’ phenotypes. Previous work has linked these phenotypes to different genetic variants, primarily present in the NAT2 gene.
The authors believe that the standard drug dose currently administered to patients, regardless of their acetylator status, may not be appropriate for certain people. Individualization of isoniazid therapy may help to prevent adverse drug reactions experienced by a small percentage of patients thought to be ‘slow-acetylators’ of the drug. Conversely fast-acetylators may not be receiving sufficient amounts of the drug to combat TB successfully, therefore increasing the likelihood of a relapse and development of drug resistance.
The authors underline the need for further research into this area. However, they believe that on confirmation of the importance of the genetics of isoniazid metabolism a simple test to determine acetylator status would be desirable and that these could be located at the same laboratories that currently perform diagnostics for TB.
