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Slow acetylator due to N-acetyltransferase enzyme variant

MedGen UID:
164207
Concept ID:
C0878587
Finding
Synonyms: Acetylation, slow; INH INACTIVATION, SLOW; ISONIAZID INACTIVATION, SLOW; SLOW ACETYLATOR PHENOTYPE
Drug:
Isoniazid
MedGen UID:
43975
Concept ID:
C0022209
Pharmacologic Substance
A synthetic derivative of nicotinic acid with anti-mycobacterial properties. Although its mechanism of action is still unclear, isoniazid appears to block the synthesis of mycolic acids, major components of the mycobacterial cell wall. This agent is only active against actively growing mycobacteria because, as a pro-drug, it requires activation in susceptible mycobacterial species. Isoniazid also interferes with mycobacterial metabolism of vitamin B6. Resistance occurs due to decreased bacterial wall penetration. (NCI04) [from NCI]
 
Gene (location): NAT2 (8p22)
 
Monarch Initiative: MONDO:0009472
OMIM®: 243400

Clinical features

From HPO
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding

Professional guidelines

PubMed

Lee J, Choi G, Yang S, Ha JE, Kim ES, Park JS, Lee K, Song J, Lee JH, Lee JI
Tuberculosis (Edinb) 2021 Mar;127:102052. Epub 2021 Jan 21 doi: 10.1016/j.tube.2021.102052. PMID: 33548864
Collins KS, Raviele ALJ, Elchynski AL, Woodcock AM, Zhao Y, Cooper-DeHoff RM, Eadon MT
Am J Nephrol 2020;51(10):764-776. Epub 2020 Sep 14 doi: 10.1159/000510433. PMID: 32927458Free PMC Article
Kotila OA, Fawole OI, Olopade OI, Ayede AI, Falusi AG, Babalola CP
Pharmacogenet Genomics 2019 Jul;29(5):106-113. doi: 10.1097/FPC.0000000000000373. PMID: 30882558Free PMC Article

Recent clinical studies

Etiology

Villapalos-García G, Zubiaur P, Ochoa D, Soria-Chacartegui P, Navares-Gómez M, Matas M, Mejía-Abril G, Casajús-Rey A, Campodónico D, Román M, Martín-Vílchez S, Candau-Ramos C, Aldama-Martín M, Abad-Santos F
Biomed Pharmacother 2023 Sep;165:115058. Epub 2023 Jun 28 doi: 10.1016/j.biopha.2023.115058. PMID: 37385211
Hong KU, Hein DW
Pharmacogenet Genomics 2023 Aug 1;33(6):136-137. Epub 2023 May 29 doi: 10.1097/FPC.0000000000000500. PMID: 37306342Free PMC Article
Habil MR, Salazar-González RA, Doll MA, Hein DW
Arch Toxicol 2023 Jun;97(6):1773-1781. Epub 2023 May 4 doi: 10.1007/s00204-023-03508-1. PMID: 37142755Free PMC Article
Collins KS, Raviele ALJ, Elchynski AL, Woodcock AM, Zhao Y, Cooper-DeHoff RM, Eadon MT
Am J Nephrol 2020;51(10):764-776. Epub 2020 Sep 14 doi: 10.1159/000510433. PMID: 32927458Free PMC Article
Kotila OA, Fawole OI, Olopade OI, Ayede AI, Falusi AG, Babalola CP
Pharmacogenet Genomics 2019 Jul;29(5):106-113. doi: 10.1097/FPC.0000000000000373. PMID: 30882558Free PMC Article

Diagnosis

El-Jaick KB, Ribeiro-Alves M, Soares MVG, Araujo GEF, Pereira GRC, Rolla VC, Mesquita JF, De Castro L
Mem Inst Oswaldo Cruz 2022;117:e210328. Epub 2022 Apr 27 doi: 10.1590/0074-02760210328. PMID: 35588539Free PMC Article
Lee J, Choi G, Yang S, Ha JE, Kim ES, Park JS, Lee K, Song J, Lee JH, Lee JI
Tuberculosis (Edinb) 2021 Mar;127:102052. Epub 2021 Jan 21 doi: 10.1016/j.tube.2021.102052. PMID: 33548864
Chan SL, Chua APG, Aminkeng F, Chee CBE, Jin S, Loh M, Gan SH, Wang YT, Brunham LR
PLoS One 2017;12(10):e0186200. Epub 2017 Oct 16 doi: 10.1371/journal.pone.0186200. PMID: 29036176Free PMC Article
Ben Fredj N, Gam R, Kerkni E, Chaabane A, Chadly Z, Boughattas N, Aouam K
Pharmacogenomics J 2017 Jul;17(4):372-377. Epub 2016 Apr 19 doi: 10.1038/tpj.2016.26. PMID: 27089936
de Lima Junior MM, Reis LO, Guilhen AC, Granja F, de Lima Oliveira MN, Ferreira U, Cunha LL, Ward LS
Med Oncol 2012 Dec;29(4):2889-94. Epub 2012 Jan 14 doi: 10.1007/s12032-012-0157-4. PMID: 22246524

Therapy

Villapalos-García G, Zubiaur P, Ochoa D, Soria-Chacartegui P, Navares-Gómez M, Matas M, Mejía-Abril G, Casajús-Rey A, Campodónico D, Román M, Martín-Vílchez S, Candau-Ramos C, Aldama-Martín M, Abad-Santos F
Biomed Pharmacother 2023 Sep;165:115058. Epub 2023 Jun 28 doi: 10.1016/j.biopha.2023.115058. PMID: 37385211
Collins KS, Raviele ALJ, Elchynski AL, Woodcock AM, Zhao Y, Cooper-DeHoff RM, Eadon MT
Am J Nephrol 2020;51(10):764-776. Epub 2020 Sep 14 doi: 10.1159/000510433. PMID: 32927458Free PMC Article
Zahra MA, Kandeel M, Aldossary SA, Al-Taher A
Biomed Res Int 2020;2020:8765347. Epub 2020 Jun 15 doi: 10.1155/2020/8765347. PMID: 32626768Free PMC Article
Kotila OA, Fawole OI, Olopade OI, Ayede AI, Falusi AG, Babalola CP
Pharmacogenet Genomics 2019 Jul;29(5):106-113. doi: 10.1097/FPC.0000000000000373. PMID: 30882558Free PMC Article
Richardson M, Kirkham J, Dwan K, Sloan DJ, Davies G, Jorgensen AL
Int J Tuberc Lung Dis 2019 Mar 1;23(3):293-305. doi: 10.5588/ijtld.18.0324. PMID: 30871660Free PMC Article

Prognosis

El-Jaick KB, Ribeiro-Alves M, Soares MVG, Araujo GEF, Pereira GRC, Rolla VC, Mesquita JF, De Castro L
Mem Inst Oswaldo Cruz 2022;117:e210328. Epub 2022 Apr 27 doi: 10.1590/0074-02760210328. PMID: 35588539Free PMC Article
Collins KS, Raviele ALJ, Elchynski AL, Woodcock AM, Zhao Y, Cooper-DeHoff RM, Eadon MT
Am J Nephrol 2020;51(10):764-776. Epub 2020 Sep 14 doi: 10.1159/000510433. PMID: 32927458Free PMC Article
Zahra MA, Kandeel M, Aldossary SA, Al-Taher A
Biomed Res Int 2020;2020:8765347. Epub 2020 Jun 15 doi: 10.1155/2020/8765347. PMID: 32626768Free PMC Article
Hemminki K, Bermejo JL, Ji J, Kumar R
Curr Opin Urol 2011 Sep;21(5):386-92. doi: 10.1097/MOU.0b013e32834958ff. PMID: 21738036
Weber WW
Birth Defects Orig Artic Ser 1990;26(1):43-65. PMID: 2224079

Clinical prediction guides

El-Jaick KB, Ribeiro-Alves M, Soares MVG, Araujo GEF, Pereira GRC, Rolla VC, Mesquita JF, De Castro L
Mem Inst Oswaldo Cruz 2022;117:e210328. Epub 2022 Apr 27 doi: 10.1590/0074-02760210328. PMID: 35588539Free PMC Article
Collins KS, Raviele ALJ, Elchynski AL, Woodcock AM, Zhao Y, Cooper-DeHoff RM, Eadon MT
Am J Nephrol 2020;51(10):764-776. Epub 2020 Sep 14 doi: 10.1159/000510433. PMID: 32927458Free PMC Article
Zahra MA, Kandeel M, Aldossary SA, Al-Taher A
Biomed Res Int 2020;2020:8765347. Epub 2020 Jun 15 doi: 10.1155/2020/8765347. PMID: 32626768Free PMC Article
Hein DW, Fakis G, Boukouvala S
Pharmacogenet Genomics 2018 Oct;28(10):238-244. doi: 10.1097/FPC.0000000000000350. PMID: 30222709Free PMC Article
Chan SL, Chua APG, Aminkeng F, Chee CBE, Jin S, Loh M, Gan SH, Wang YT, Brunham LR
PLoS One 2017;12(10):e0186200. Epub 2017 Oct 16 doi: 10.1371/journal.pone.0186200. PMID: 29036176Free PMC Article

Recent systematic reviews

Richardson M, Kirkham J, Dwan K, Sloan DJ, Davies G, Jorgensen AL
Int J Tuberc Lung Dis 2019 Mar 1;23(3):293-305. doi: 10.5588/ijtld.18.0324. PMID: 30871660Free PMC Article

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