Skip to Main content Skip to Navigation
Theses

Etude du polymorphisme génétique de la N-Acétyltransférase de type 2 dans la population sénégalaise : prévention de la toxicité et de l’échec thérapeutique de l’isoniazide dans la prise en charge de la tuberculose

Abstract : Xenobiotic biotransformation undergoes several stages of simultaneous or successive whose main attractions are the tissues at the interface between the organism and the external environment, namely: digestive, respiratory, kidney and liver. The latter being the most important functionally. The reaction phases constituting the main stages of detoxification, phase I, phase II and phase III, are possible only through the intervention of specific enzyme systems. Given the wide diversity of xenobiotics to which the organism is exposed, there are a multitude of enzymes with various specificities. The biotransformation reactions of xenobiotics are linked linearly rarely, because two or more lanes are often born from a given metabolite. It is therefore understandable that the existence of an enzyme variant defective for one of these reaction pathways can direct the metabolism of a given substance to another track. The latter, usually minor, will therefore important and polymorphisms that concern will guide the fate of metabolites thus formed. The N-acetyltransferases (NATs) is part of enzymes that primarily the conjugation reaction of phase II detoxification of xenobiotics. The polymorphism of NATS is one of the examples of pharmacogenetic variation described, and one of the most documented since its discovery in the early \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'50s, along with the discovery of the high efficacy of isoniazid (INH) in the treatment of tuberculosis. The work of this thesis aimed to study the profile of the NAT2 acetylation in the Senegalese population in order to distribute them in slow acetylators and rapid acetylators, and determine the kinetics of isoniazid in tuberculous subjects correlated with the results of genotyping. The study of mutations of the NAT2 gene was performed by PCR-direct sequencing and allowed to identify 11 allelic variants in the Senegalese population. The enzymatic activity of NAT2 was determined by using caffeine test and the ratios of major metabolites allowed Senegalese classify fast and slow acetylators. The kinetics of isoniazid used UPLC-MS/MS chromatography.
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-00872736
Contributor : Abes Star :  Contact
Submitted on : Monday, October 14, 2013 - 1:03:08 PM
Last modification on : Tuesday, December 1, 2020 - 3:12:04 PM
Long-term archiving on: : Wednesday, January 15, 2014 - 6:00:17 AM

File

2012LIL2S042.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00872736, version 1

Collections

Citation

Aminata Touré. Etude du polymorphisme génétique de la N-Acétyltransférase de type 2 dans la population sénégalaise : prévention de la toxicité et de l’échec thérapeutique de l’isoniazide dans la prise en charge de la tuberculose. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2012. Français. ⟨NNT : 2012LIL2S042⟩. ⟨tel-00872736⟩

Share

Metrics

Record views

675

Files downloads

7664