Background: Tuberculosis is one of the most prevalent infectious diseases.
Treatment of tuberculosis requires treatment for a long duration with a combination of
drugs such as Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. Certain subsets of the
population are more susceptible to adverse effects of treatment with isoniazid. Identification
of the related genetic polymorphisms will enable Personalized Medication with optimized
combination and dosage of the available drugs for each individual.
Objective: Identification of the molecular targets responsible for differences in susceptibility
to the adverse effects of isoniazid drug.
Method: Inverse docking was used to identify potential molecular targets of isoniazid in
the human proteome. The molecular targets and the annotations obtained from inverse
docking were compared with those obtained from PharmGKB variant annotations.
Results and Conclusion: The results of this study are consistent with and rationalize earlier
biochemical, molecular and clinical studies that relate prevalence of isoniazid induced
adverse effects to genetic polymorphisms in NAT2, GSTT1, GSTM1 and CYP*. The
computational results of this study indicate that MAO, COMT and NNMT are additional
potential targets related to variation in isoniazid induced adverse effects.