Skip to main content
Log in

Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

Previous studies have demonstrated a strong association between carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and HLA-B*1502 in Han Chinese. Here, we extended the study of HLA-B*1502 susceptibility to two different antiepileptic drugs, oxcarbazepine (OXC) and phenobabital (PB). In addition, we genotyped HLA-B*1511 in a case of CBZ-induced SJS with genotype negative for HLA-B*1502. The presence of HLA-B*1502 was determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). Moreover, we genotyped HLA-B*1502 in 17 cases of antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs), in comparison with AEDs-tolerant (n=32) and normal controls (n=38) in the central region of China. The data showed that HLA-B*1502 was positive in 5 of 6 cases of AEDs-induced SJS (4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant (2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls (3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B*1502 with AEDs-induced SJS was 6.25 (95% CI: 1.06–36.74) and 4.86 (95% CI: 1.01–23.47). The sensitivity and specificity of HLA-B*1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B*1502 was not found in 11 children with maculopapular exanthema (MPE) (n=9) and hypersensitivity syndrome (HSS) (n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B*1502 but carried HLA-B*1511. It was suggested that the association between the CBZ-induced SJS and HLA-B*1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B*1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B*1502.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. New Engl J Med, 1994,331(19):1272–1285

    Article  CAS  PubMed  Google Scholar 

  2. Hung SI, Chung WH, Jee SH, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics, 2006,16(4):297–306

    Article  CAS  PubMed  Google Scholar 

  3. Lim KS, Kwan P, Tan CT. Association of HLA-B*1502 allele and carbamazepine-induced severe adverse cutaneous drug reaction among Asians, a review. Neurology Asia, 2008,13(6):15–21

    Google Scholar 

  4. Chang CC, Too CL, Murad S, et al. Association of HLAB*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population. Int J Dermatol, 2011,50(2):221–224

    Article  PubMed  Google Scholar 

  5. Ozeki T, Mushiroda T, Yowang A, et al. Genome-wide association study identifies HLAA*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet, 2011,20(5):1034–1041

    Article  CAS  PubMed  Google Scholar 

  6. Man CB, Kwan P, Baum L, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia, 2007,48(5): 1015–1018

    Article  CAS  PubMed  Google Scholar 

  7. Bunce M, O’Neill CM, Barnardo MC, et al. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens, 1995,46(5):355–367

    Article  CAS  PubMed  Google Scholar 

  8. Lonjou C, Thomas L, Borot N, et al. RegiSCAR Group. A marker for Stevens-Johnson syndrome ethnicity matters. Pharmacogenomics J, 2006,6(4):265–268

    CAS  PubMed  Google Scholar 

  9. Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature, 2004,428(6982):486

    Article  CAS  PubMed  Google Scholar 

  10. Locharernkul C, Loplumlert J, Limotai C, et al. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia, 2008,49(12):2087–2091

    Article  PubMed  Google Scholar 

  11. Ikeda H, Takahashi Y, Yamazaki E, et al. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia, 2010,51(2): 297–300

    Article  PubMed  Google Scholar 

  12. Alfirevic A, Jorgensen AL, Williamson PR, et al. HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics, 2006,7(6):813–818

    Article  CAS  PubMed  Google Scholar 

  13. Mehta TY, Prajapati LM, Mittal B, et al. Association of HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians. Indian J Dermatol Venereol Leprol, 2009,75(6):579–582

    Article  PubMed  Google Scholar 

  14. Wu XT, Hu FY, An DM, et al. Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients. Epilepsy Behav, 2010,19(3):405–408

    Article  CAS  PubMed  Google Scholar 

  15. Tassaneeyakul W, Tiamkao S, Jantararoungtong T, et al. Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia, 2010,51(5):926–930

    Article  PubMed  Google Scholar 

  16. Zhang Y, Wang J, Zhao LM, et al. Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients. Eur J Clin Pharmacol, 2011,67(9):885–887

    Article  PubMed  Google Scholar 

  17. Wang Q, Zhou JQ, Zhou LM, et al. Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland. Seizure, 2011,20(6):446–448

    Article  PubMed  Google Scholar 

  18. Shi YW, Min FL, Qin B, et al. Association between HLA and Stevens-Johnson syndrome induced by carbamazepine in Southern Han Chinese: genetic markers besides B*1502? Basic Clin Pharmacol Toxicol, 2012,111(1):58–64

    CAS  PubMed  Google Scholar 

  19. Kulkantrakorn K, Tassaneeyakul W, Tiamkao S, et al. HLA-B*1502 strongly predicts carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Thai patients with neuropathic pain. Pain Pract, 2012,12(3):202–208

    Article  PubMed  Google Scholar 

  20. Kaniwa N, Saito Y, Aihara M, 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(12):2461–2465

    Article  CAS  PubMed  Google Scholar 

  21. Knowles SR, Shapiro LE, Shear NH. Anticonvulsion hypersensitivity syndrome: incidence, prevention and management. Drug Saf, 1999,21(6):489–501

    Article  CAS  PubMed  Google Scholar 

  22. Hirsch LJ, Arif H, Nahm EA, et al. Cross-sensitivity of skin rashes with antiepileptic drug use. Neurology, 2008,71(19),1527–1534

    Article  CAS  PubMed  Google Scholar 

  23. Alvestad S, Lydersen S, Brodtkorb E. Cross-reactivity pattern of rash from current aromatic antiepileptic drugs. Epilepsy Res, 2008,80(23):194–200

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

These authors contributed equally to this work.

This study was supported by a grant from Clinical Scientific Research of Wuhan Sanitary Bureau (No. WX11C26) and research fund from Janssen Research Council of China (No. JRCC2011-01).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, D., Yu, Ch., Liu, Zs. et al. Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 146–150 (2014). https://doi.org/10.1007/s11596-014-1247-7

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-014-1247-7

Key words

Navigation