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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

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
Torkaman-Boutorabi A, Hoormand M, Naghdi N, Bakhshayesh M, Milanian I
Clin Exp Pharmacol Physiol 2007 Nov;34(11):1207-11. doi: 10.1111/j.1440-1681.2007.04753.x. PMID: 17880378

Recent clinical studies

Etiology

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
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
Hemminki K, Bermejo JL, Ji J, Kumar R
Curr Opin Urol 2011 Sep;21(5):386-92. doi: 10.1097/MOU.0b013e32834958ff. PMID: 21738036
Bouchardy C, Mitrunen K, Wikman H, Husgafvel-Pursiainen K, Dayer P, Benhamou S, Hirvonen A
Pharmacogenetics 1998 Aug;8(4):291-8. doi: 10.1097/00008571-199808000-00002. PMID: 9731715

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
Walia HK, Singh N, Sharma S
Pharmacogenomics 2022 Jan;23(2):97-118. Epub 2021 Dec 16 doi: 10.2217/pgs-2021-0080. PMID: 34911343
Xiang Y, Ma L, Wu W, Liu W, Li Y, Zhu X, Wang Q, Ma J, Cao M, Wang Q, Yao X, Yang L, Wubuli A, Merle C, Milligan P, Mao Y, Gu J, Xin X
PLoS One 2014;9(1):e85905. Epub 2014 Jan 23 doi: 10.1371/journal.pone.0085905. PMID: 24465778Free PMC Article
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
Schnakenberg E, Fabig KR, Stanulla M, Strobl N, Lustig M, Fabig N, Schloot W
Environ Health 2007 Feb 10;6:6. doi: 10.1186/1476-069X-6-6. PMID: 17291352Free PMC Article

Therapy

Yoo H, Chun Ji S, Cho JY, Kim SH, Yoon JG, Goo Lee M, Yu KS, Jang IJ, Oh J
Pharmacogenet Genomics 2021 Apr 1;31(3):68-73. doi: 10.1097/FPC.0000000000000423. PMID: 33165168
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
Adole PS, Kharbanda PS, Sharma S
Indian J Med Res 2016 May;143(5):581-90. doi: 10.4103/0971-5916.187106. PMID: 27488001Free PMC Article
Guaoua S, Ratbi I, Laarabi FZ, Elalaoui SC, Jaouad IC, Barkat A, Sefiani A
BMC Genet 2014 Dec 29;15:156. doi: 10.1186/s12863-014-0156-x. PMID: 25544508Free PMC Article

Prognosis

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
Guaoua S, Ratbi I, Laarabi FZ, Elalaoui SC, Jaouad IC, Barkat A, Sefiani A
BMC Genet 2014 Dec 29;15:156. doi: 10.1186/s12863-014-0156-x. PMID: 25544508Free PMC Article
Xiang Y, Ma L, Wu W, Liu W, Li Y, Zhu X, Wang Q, Ma J, Cao M, Wang Q, Yao X, Yang L, Wubuli A, Merle C, Milligan P, Mao Y, Gu J, Xin X
PLoS One 2014;9(1):e85905. Epub 2014 Jan 23 doi: 10.1371/journal.pone.0085905. PMID: 24465778Free 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

Walia HK, Singh N, Sharma S
Pharmacogenomics 2022 Jan;23(2):97-118. Epub 2021 Dec 16 doi: 10.2217/pgs-2021-0080. PMID: 34911343
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
Hein DW, Fakis G, Boukouvala S
Pharmacogenet Genomics 2018 Oct;28(10):238-244. doi: 10.1097/FPC.0000000000000350. PMID: 30222709Free PMC Article
Pistorius S, Görgens H, Krüger S, Engel C, Mangold E, Pagenstecher C, Holinski-Feder E, Moeslein G, von Knebel Doeberitz M, Rüschoff J, Karner-Hanusch J, Saeger HD, Schackert HK; German Hnpcc-Consortium
Cancer Lett 2006 Sep 8;241(1):150-7. Epub 2005 Dec 6 doi: 10.1016/j.canlet.2005.10.018. PMID: 16337339
Bouchardy C, Mitrunen K, Wikman H, Husgafvel-Pursiainen K, Dayer P, Benhamou S, Hirvonen A
Pharmacogenetics 1998 Aug;8(4):291-8. doi: 10.1097/00008571-199808000-00002. PMID: 9731715

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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