N-acetyltransferase 2, cytochrome P4502E1 and glutathione S-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians

S V Rana, S K Sharma, R P Ola, J K Kamboj, A Malik, R K Morya, S K Sinha
Journal of Clinical Pharmacy and Therapeutics 2014, 39 (1): 91-6

WHAT IS KNOWN AND OBJECTIVE: Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S-transferase (GST) gene polymorphisms may play an important role in ATT-induced hepatotoxicity. So, elucidating the genetics involved in anti-TB drug-induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT-induced hepatotoxicity in North Indian patients.

METHODS: Three hundred patients with pulmonary and extra-pulmonary TB were enrolled. Total genomic DNA was isolated from each patient's peripheral lymphocytes using phenol-chloroform method, and genetic polymorphic analysis for N-acetyltransferase 2 (NAT2), cytochrome P4502E1 (CYP2E1) and GST was performed by polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP).

RESULTS AND DISCUSSION: Of the 300 patients, 185 were males and 115 females. Among them, 33 males and 22 females developed ATT-induced hepatotoxicity. There were significant increases in alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with ATT-induced hepatotoxicity at 1 month of treatment. NAT2 5/7 and 6/7 were significantly higher in hepatotoxicity patients as compared to the non-hepatotoxicity group. c1/c1 allele of CYP2E1 gene was lower (50·9%) in ATT-induced hepatotoxicity patients as compared to non-hepatotoxicity patients (61·2%), whereas c1/c2 and c2/c2 alleles were higher, but not statistically significant. GSTM1 was significantly higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, whereas GSTT1 and GSTT1/M1 were lower, but not statistically significant.

WHAT IS NEW AND CONCLUSION: This study indicates that patients with slow-acetylator genotypes (NAT2 5/7, 6/7) and GSTM1 allele of GST enzyme were at higher risk of ATT-induced hepatotoxicity.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"