Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

Surendra K. Sharma; Brajesh Kumar Jha; Abhishek Sharma; V. Sreenivas; Vishwanath Upadhyay; Chandrita Jaisinghani; Rohit Singla; Hemant Kumar Mishra; Manish Soneja

doi:10.4103/ijmr.IJMR_684_14

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

Surendra K. Sharma, Brajesh Kumar Jha, Abhishek Sharma, V. Sreenivas, Vishwanath Upadhyay, Chandrita Jaisinghani, Rohit Singla, Hemant Kumar Mishra, Manish Soneja

Veterinary and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Background & objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2*5/*7 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Original language	English (US)
Pages (from-to)	924-928
Number of pages	5
Journal	Indian Journal of Medical Research
Volume	144
Issue number	DECEMBER
DOIs	https://doi.org/10.4103/ijmr.IJMR_684_14
State	Published - Dec 2016

Bibliographical note

Funding Information:
Authors thank the clinical, laboratory and administrative staff and patients of the AIIMS, New Delhi, for their support. This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi (Grant number BT/PR7885/MED/14/1166/2006). The first author (SKS) was supported by JC Bose Fellowship [Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi (No. SB/S2/JCB-04/2013)].

Publisher Copyright:
© 2017, Indian Council of Medical Research. All rights reserved.

Keywords

Drug-induced hepatotoxicity
Genetic polymorphism
N-acetyltransferase 2
Polymerase chain reaction
Rapid acetylator
Restriction fragment length polymorphism
Slow acetylator

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity",

abstract = "Background & objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2*5/*7 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.",

keywords = "Drug-induced hepatotoxicity, Genetic polymorphism, N-acetyltransferase 2, Polymerase chain reaction, Rapid acetylator, Restriction fragment length polymorphism, Slow acetylator",

author = "Sharma, {Surendra K.} and Jha, {Brajesh Kumar} and Abhishek Sharma and V. Sreenivas and Vishwanath Upadhyay and Chandrita Jaisinghani and Rohit Singla and Mishra, {Hemant Kumar} and Manish Soneja",

note = "Funding Information: Authors thank the clinical, laboratory and administrative staff and patients of the AIIMS, New Delhi, for their support. This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi (Grant number BT/PR7885/MED/14/1166/2006). The first author (SKS) was supported by JC Bose Fellowship [Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi (No. SB/S2/JCB-04/2013)]. Publisher Copyright: {\textcopyright} 2017, Indian Council of Medical Research. All rights reserved.",

year = "2016",

month = dec,

doi = "10.4103/ijmr.IJMR_684_14",

language = "English (US)",

volume = "144",

pages = "924--928",

journal = "Indian Journal of Medical Research",

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T1 - Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

AU - Sharma, Surendra K.

AU - Jha, Brajesh Kumar

AU - Sharma, Abhishek

AU - Sreenivas, V.

AU - Upadhyay, Vishwanath

AU - Jaisinghani, Chandrita

AU - Singla, Rohit

AU - Mishra, Hemant Kumar

AU - Soneja, Manish

N1 - Funding Information: Authors thank the clinical, laboratory and administrative staff and patients of the AIIMS, New Delhi, for their support. This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi (Grant number BT/PR7885/MED/14/1166/2006). The first author (SKS) was supported by JC Bose Fellowship [Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi (No. SB/S2/JCB-04/2013)]. Publisher Copyright: © 2017, Indian Council of Medical Research. All rights reserved.

PY - 2016/12

Y1 - 2016/12

N2 - Background & objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2*5/*7 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

AB - Background & objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2*5/*7 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

KW - Drug-induced hepatotoxicity

KW - Genetic polymorphism

KW - N-acetyltransferase 2

KW - Polymerase chain reaction

KW - Rapid acetylator

KW - Restriction fragment length polymorphism

KW - Slow acetylator

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SN - 0971-5916

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JO - Indian Journal of Medical Research

JF - Indian Journal of Medical Research

IS - DECEMBER

ER -

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

Abstract

Bibliographical note

Keywords

UN SDGs

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