open access

Vol 75, No 2 (2007)
ORIGINAL PAPERS
Published online: 2007-06-03
Submitted: 2013-02-22
Get Citation

Detection of mutation in NAT II gene as a method of determination of izoniazyd (INH) acetylation type in human population

Ewa Augustynowicz-Kopeć, Anna Zabost, Monika Kozińska, Sylwia Brzezińska, Zofia Zwolska
Pneumonol Alergol Pol 2007;75(2):134-139.

open access

Vol 75, No 2 (2007)
ORIGINAL PAPERS
Published online: 2007-06-03
Submitted: 2013-02-22

Abstract


Introduction: Isoniazid (INH) is a drug widely used in the treatment of tuberculosis. INH is metabolized to acetylisoniazid by N-acetyltransferase (NAT) in the liver. The rate of INH acetylation is genetically determined. NAT isozymes are encoded at 2 loci; one encodes NAT1, formerly known as the monomorphic form of the enzyme, while the other encodes the polymorphic NAT2, which is responsible for individual differences in the ability to acetylate certain compounds. The objective of the present study was to apply the genotyping of the fast and slow acetylators for personalized therapeutic dose.
Material and methods: Plasma concentrations of INH were determined with biological method in the authors modification. This method warrants high accuracy and secured repeatable results. Genomic DNA was isolated from the blood samples. DNA extracted by Blood DNA Kit and amplified by PCR by Spurr [1] with two primers. PCR product was cut separately with 4 different restriction enzymes: Dde1, Kpn1, Tag1, and BamH1.
Results: Four different NAT 2 alleles were detected in the study population. The presence of any 2 mutant alleles defines the slow-acetylator genotype, whereas rapid acetylators have 1 or 2 wild-type NAT2*4 alleles.
Conclusion: On the basis of our results we suggest the using of NAT 2 genotyping for discrimination of the fast and slow acetylators in monitoring of tuberculosis therapy.

Abstract


Introduction: Isoniazid (INH) is a drug widely used in the treatment of tuberculosis. INH is metabolized to acetylisoniazid by N-acetyltransferase (NAT) in the liver. The rate of INH acetylation is genetically determined. NAT isozymes are encoded at 2 loci; one encodes NAT1, formerly known as the monomorphic form of the enzyme, while the other encodes the polymorphic NAT2, which is responsible for individual differences in the ability to acetylate certain compounds. The objective of the present study was to apply the genotyping of the fast and slow acetylators for personalized therapeutic dose.
Material and methods: Plasma concentrations of INH were determined with biological method in the authors modification. This method warrants high accuracy and secured repeatable results. Genomic DNA was isolated from the blood samples. DNA extracted by Blood DNA Kit and amplified by PCR by Spurr [1] with two primers. PCR product was cut separately with 4 different restriction enzymes: Dde1, Kpn1, Tag1, and BamH1.
Results: Four different NAT 2 alleles were detected in the study population. The presence of any 2 mutant alleles defines the slow-acetylator genotype, whereas rapid acetylators have 1 or 2 wild-type NAT2*4 alleles.
Conclusion: On the basis of our results we suggest the using of NAT 2 genotyping for discrimination of the fast and slow acetylators in monitoring of tuberculosis therapy.
Get Citation

Keywords

N-acetyltransferase; isoniazid; polymorphism NAT II; treatment of tuberculosis

About this article
Title

Detection of mutation in NAT II gene as a method of determination of izoniazyd (INH) acetylation type in human population

Journal

Advances in Respiratory Medicine

Issue

Vol 75, No 2 (2007)

Pages

134-139

Published online

2007-06-03

Bibliographic record

Pneumonol Alergol Pol 2007;75(2):134-139.

Keywords

N-acetyltransferase
isoniazid
polymorphism NAT II
treatment of tuberculosis

Authors

Ewa Augustynowicz-Kopeć
Anna Zabost
Monika Kozińska
Sylwia Brzezińska
Zofia Zwolska

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Czasopismo Pneumonologia i Alergologia Polska dostęne jest również w Ikamed - księgarnia medyczna

Wydawcą serwisu jest "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl