Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Avoidance of cutaneous adverse drug reactions induced by antiepileptic drugs based on pharmacogenomics

Journal of Human Genetics volume 68, pages 227–230 (2023)Cite this article

Subjects

Abstract

Pharmacogenomics (PGx) is a research area aimed at identifying genetic factors that are associated with drug responses, including drug efficacy, adverse drug reactions, and the appropriate drug dosage on a case-to-case basis. To promote the clinical implementation of PGx testing, which is currently of limited use in clinical practice, recent research has focused on providing reliable evidence for its clinical utility. In neurology, psychiatry, and neurosurgery, several human leukocyte antigen (HLA) alleles have been reportedly associated with cutaneous adverse drug reactions (cADRs) induced by antiepileptic drugs, which significantly carry the risk of developing cADRs. Prior to using antiepileptic drugs such as carbamazepine and lamotrigine, which are prone to cause severe cADRs, preemptive HLA genetic testing and therapeutic interventions such as drug selection and dosage adjustment based on the results of the tests can reduce the incidence of cADRs in the population before the initiation of treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Pharmaceuticals and Medical Devices Agency, Japan. Annual Report FY 2019. Available from https://www.pmda.go.jp/files/000240772.pdf.

  2. Pharmaceutical and food safety bureau, Ministry of Health, Labour and Welfare, Japan. Pharmaceuticals and Medical Devices Safety Information 2012. Available from https://www.pmda.go.jp/files/000153540.pdf.

  3. Yang SC, Chen CB, Lin MY, Zhang ZY, Jia XY, Huang M, et al. Genetics of severe cutaneous adverse reactions. Front Med (Lausanne). 2021;8:652091.

    Article  Google Scholar 

  4. Matzaraki V, Kumar V, Wijmenga C, Zhernakova A. The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biol. 2017;18:76.

    Article  Google Scholar 

  5. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens–Johnson syndrome. Nature 2004;428:486.

    Article  CAS  Google Scholar 

  6. Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M, Shirakata Y, et al. Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in a Japanese population. population. Hum Mol Genet. 2011;20:1034–41.

    Article  CAS  Google Scholar 

  7. McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiūtė D, Carrington M, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N. Engl J Med. 2011;364:1134–43.

    Article  CAS  Google Scholar 

  8. Deng Y, Li S, Zhang L, Jin H, Zou X. Association between HLA alleles and lamotrigine-induced cutaneous adverse drug reactions in Asian populations: a meta-analysis. Seizure 2018;60:163–71.

    Article  Google Scholar 

  9. Manuyakorn W, Siripool K, Kamchaisatian W, Pakakasama S, Visudtibhan A, Vilaiyuk S, et al. Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children. Pediatr Allergy Immunol. 2013;24:299–303.

    Article  Google Scholar 

  10. Kaniwa N, Sugiyama E, Saito Y, Kurose K, Maekawa K, Hasegawa R, et al. Specific HLA types are associated with antiepileptic drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics 2013;14:1821–31.

    Article  CAS  Google Scholar 

  11. Guberman AH, Besag FM, Brodie MJ, Dooley JM, Duchowny MS, Pellock JM, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia 1999;40:985–91.

    Article  CAS  Google Scholar 

  12. Alfares I, Javaid MS, Chen Z, Anderson A, Antonic-Baker A, Kwan P. Sex differences in the risk of cutaneous adverse drug reactions induced by antiseizure medications: A systematic review and meta-analysis. CNS Drugs. 2021;35:161–76.

    Article  Google Scholar 

  13. Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, Yang CC, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N. Engl J Med. 2011;364:1126–33.

    Article  CAS  Google Scholar 

  14. Mushiroda T, Takahashi Y, Onuma T, Yamamoto Y, Kamei T, Hoshida T, et al. Association of HLA-A*31:01 Screening With the Incidence of Carbamazepine-Induced Cutaneous Adverse Reactions in a Japanese Population. JAMA Neurol Assoc HLA-A. 2018;75:842–9.

    Article  Google Scholar 

  15. Tashiro Y, Azukizawa H, Asada H, Niihara H, Morita E, Yamauchi T, et al. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs. J Dermatol. 2019;46:226–33.

    Article  CAS  Google Scholar 

  16. Su SC, Chen CB, Chang WC, Wang CW, Fan WL, Lu LY, et al. HLA alleles and CYP2C9*3 as predictors of phenytoin hypersensitivity in East Asians. Clin Pharm Ther. 2019;105:476–85.

    Article  CAS  Google Scholar 

  17. Hikino K, Ozeki T, Koido M, Terao C, Kamatani Y, Mizukawa Y, et al. HLA-B*51:01 And CYP2C9*3 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: Analysis of Data from the Biobank Japan Project. Clin Pharm Ther. 2020;107:1170–8.

    Article  CAS  Google Scholar 

  18. Chang CC, Too CL, Murad S, Hussein SH. Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens–Johnson syndrome in the multi-ethnic Malaysian population. Int J Dermatol. 2011;50:221–4.

    Article  Google Scholar 

  19. Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, et al. Carbamazepine and phenytoin induced Stevens–Johnson syndrome is associated with HLA-B*1502 allele in a Thai population. Epilepsia 2008;49:2087–91.

    Article  Google Scholar 

  20. Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 2007;48:1015–8.

    Article  CAS  Google Scholar 

  21. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, et al. HLA-B*1511 is a risk factor for carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Epilepsia 2010;51:2461–5.

    Article  CAS  Google Scholar 

  22. Mockenhaupt M, Wang CW, Hung SI, Sekula P, Schmidt AH, Pan RY, et al. HLA-B*57:01 confers genetic susceptibility to carbamazepine-induced SJS/TEN in Europeans. Allergy 2019;74:2227–30.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the Project for Development of Innovative Research on Cancer Therapeutics and Tailor-made Medical Treatment Program (BioBank Japan Project) funded by the Ministry of Education, Culture, Sports, Science, and Technology of Japan and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare of Japan (H26-nanchi(nan)-ippan-081).

Author information

Authors and Affiliations

  1. Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan

    Taisei Mushiroda

Authors
  1. Taisei Mushiroda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Taisei Mushiroda.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mushiroda, T. Avoidance of cutaneous adverse drug reactions induced by antiepileptic drugs based on pharmacogenomics. J Hum Genet 68, 227–230 (2023). https://doi.org/10.1038/s10038-022-01040-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s10038-022-01040-1

Search

Advanced search

Quick links