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Ahmed AF, Sukasem C, Sabbah MA, et al. Genetic Determinants in . J Pers Med. 2021;11(5)doi: 10.3390/jpm11050383.
Ahmed, A. F., Sukasem, C., Sabbah, M. A., Musa, N. F., Mohamed Noor, D. A., & Daud, N. A. A. (2021). Genetic Determinants in . Journal of personalized medicine, 11(5), . https://doi.org/10.3390/jpm11050383
Ahmed, Ali Fadhel, et al. "Genetic Determinants in ." Journal of personalized medicine vol. 11,5 (2021). doi: https://doi.org/10.3390/jpm11050383
Ahmed AF, Sukasem C, Sabbah MA, Musa NF, Mohamed Noor DA, Daud NAA. Genetic Determinants in . J Pers Med. 2021 May 07;11(5). doi: 10.3390/jpm11050383. PMID: 34067134; PMCID: PMC8150699.
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J Pers Med. 2021 May 07;11(5). doi: 10.3390/jpm11050383.

Genetic Determinants in .

Journal of personalized medicine

Ali Fadhel Ahmed, Chonlaphat Sukasem, Majeed Arsheed Sabbah, Nur Fadhlina Musa, Dzul Azri Mohamed Noor, Nur Aizati Athirah Daud

Affiliations

  1. Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800, Malaysia.
  2. Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
  3. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok 10400, Thailand.
  4. The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group, Chulalongkorn University, Bangkok 10330, Thailand.
  5. Advanced Research and Development Laboratory, Bumrungrad International Hospital, Bangkok 10110, Thailand.
  6. Forensic DNA for Research and Training Centre, Alnahrain University, Baghdad 64074, Iraq.
  7. Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia.

PMID: 34067134 PMCID: PMC8150699 DOI: 10.3390/jpm11050383

Abstract

Adverse drug reaction (ADR) is a pressing health problem, and one of the main reasons for treatment failure with antiepileptic drugs. This has become apparent in the event of severe cutaneous adverse reactions (SCARs), which can be life-threatening. In this review, four hypotheses were identified to describe how the immune system is triggered in the development of SCARs, which predominantly involve the human leukocyte antigen (HLA) proteins. Several genetic variations in HLA genes have been shown to be strongly associated with the susceptibility to developing SCARs when prescribed carbamazepine or phenytoin. These genetic variations were also shown to be prevalent in certain populations. Apart from the HLA genes, other genes proposed to affect the risk of SCARs are genes encoding for CYP450 drug-metabolising enzymes, which are involved in the pharmacokinetics of offending drugs. Genetic variants in CYP2C9 and CYPC19 enzymes were also suggested to modulate the risk of SCARs in some populations. This review summarizes the literature on the manifestation and aetiology of antiepileptic-induced SCARs, updates on pharmacogenetic markers associated with this reaction and the implementation of pre-emptive testing as a preventive strategy for SCARs.

Keywords: CYP450 enzymes; HLA; SCAR; antiepileptics; cutaneous adverse drug reaction; genetic polymorphism

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