The pharmacogenomics in the personalization of isoniazid treatment of patients with tuberculosis

Tuberculosis is still a leading cause of death from infectious disease worldwide. Isoniazid (INH) is a pivotal agent in the treatment of tuberculosis, included in all therapeutic protocols, but is also the most prevalent cause of drug-induced hepatotoxicity (DILI), an adverse effect occurring in 10-36% of patients and possibly fatal. The major aim of the project was to evaluate the repercussion of personalization of INH dosing by NAT2 genotyping in the management of tuberculosis patients. We also assessed the role of other candidate genes like CYP2E1 , GSTM1 and GSTT1, encoding detoxifying enzymes, and ABCB11 , encoding a protein involved in bile salt transport. Two groups of tuberculosis patients, 111 without analytical evidence of hepatotoxicity and 56 that developed hepatotoxicity, were compared. Patients had a mean age of 47 years old (sd-16.83) and included 58 females. Clinical variables such as gender and age were not associated with the occurrence of INH-induced hepatitis. Slow acetylators (52.3%), identified by NAT2 genotyping, were significantly more prone to develop hepatotoxicity (( p ABCB11 polymorphism (rs2287622) (p The presence of both risk genotypes was also significantly associated with increased susceptibility to hepatotoxicity (p NAT2 ), 32% of Ala/Ala ( ABCB11 ) and 21% with both risk genotypes9. Results should be confirmed and prospective studies performed to evaluate if genotyping should be implemented in the management of tuberculosis patients.