Pharmacogenetic testing for NAT2 genotypes in a Tanzanian population across the lifespan to guide future personalized isoniazid dosing.
Acetylation
Isoniazid
N-acetyltransferase
Pharmacogenetics
Pharmacokinetics
Journal
Tuberculosis (Edinburgh, Scotland)
ISSN: 1873-281X
Titre abrégé: Tuberculosis (Edinb)
Pays: Scotland
ID NLM: 100971555
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
12
04
2022
revised:
12
07
2022
accepted:
03
08
2022
pubmed:
13
8
2022
medline:
28
9
2022
entrez:
12
8
2022
Statut:
ppublish
Résumé
Despite updated recommendations for weight-based isoniazid dosing in children with drug-susceptible tuberculosis (TB) and higher dose isoniazid in regimens for adults with drug-resistant TB, individual pharmacokinetic variability can lead to sub-target isoniazid exposure. Host pharmacogenetics and isoniazid exposure remain understudied, especially in the East African population. We therefore employed a real-time polymerase chain reaction (qPCR) assay system to test genomic DNA extracted from saliva samples targeting the NAT2 gene responsible for isoniazid metabolism to describe the frequency of human single nucleotide polymorphisms in NAT2 within populations of children and adults in Tanzania, ascribe those polymorphisms to acetylator phenotype, and correlate to serum isoniazid exposures. In adults treated with higher dose isoniazid, genotypes with a predicted allelic phenotype of slow or intermediate acetylation were able to achieve a 0.41 μg/mL higher C
Identifiants
pubmed: 35961094
pii: S1472-9792(22)00083-X
doi: 10.1016/j.tube.2022.102246
pmc: PMC9884397
mid: NIHMS1851587
pii:
doi:
Substances chimiques
Antitubercular Agents
0
Arylamine N-Acetyltransferase
EC 2.3.1.5
Isoniazid
V83O1VOZ8L
NAT2 protein, human
EC 2.3.1.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102246Subventions
Organisme : FIC NIH HHS
ID : D43 TW006578
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI115594
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Ltd.
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