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Erschienen in: Zeitschrift für Epileptologie 4/2012

01.11.2012 | Original Contribution

The association between AED-induced cutaneous adverse drug reactions and the HLA-A, -B, and -DRB1 alleles among Caucasian patients: a pilot multicenter study

verfasst von: X. Wu, W. Graf, F.C. Schmitt, G. Kurlemann, W.S. Kunz, M. Heers, B. Kasper, H. Hamer, D. Zhou, Prof. H. Stefan

Erschienen in: Clinical Epileptology | Ausgabe 4/2012

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Abstract

Background

A strong association has been reported between HLA-B*1502 and severe cutaneous adverse drug reactions (CADRs) induced by carbamazepine (CBZ) in Han Chinese patients. However, some investigations showed that the HLA-B*1502 allele is not the universal marker for CADRs in European patients. Moreover, HLA-A*3101 was found to be associated with CBZ-induced hypersensitivity reactions among subjects of northern European ancestry.

Objective

This study aimed to find out the correlation between the human leukocyte antigen (HLA-A, -B, and -DRB1) alleles and antiepileptic drug (AED)-induced CADRs in Caucasian patients.

Design and methods

Sixteen patients with AED-induced mild CADRs and eight AED-tolerant controls were enrolled. HLA genotyping was performed by the polymerase chain reaction (PCR) sequence-based typing (SBT) method.

Results

On the basis of frequency, 13 HLA-A alleles, 15 HLA-B, and 15 HLA-DRB1 alleles were detected by genotyping. HLA-B*1502 was not detected in any of the subjects. In the CADRs group, HLA-B*0801 had the highest frequency compared with other alleles, without a statistical difference between CADRs and the AED-tolerant group. Only two patients with CADRs had the HLA-A*3101 allele.

Conclusion

HLA-B*1502 is probably not the genetic marker for Caucasian patients with AED-induced CADRs. The frequency of HLA-B*0801 was highest in patients with AED-induced mild CADRs. Nevertheless, statistically, no confirmed correlation between HLA-A, -B, and -DRB1 and Caucasian patients with AED-induced CADRs could be made. Because the number of Caucasian subjects was limited in this pilot study, further studies are planned in Germany.
Literatur
1.
Zurück zum Zitat Mockenhaupt M, Viboud C, Dunant A et al (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 128:35–44PubMedCrossRef Mockenhaupt M, Viboud C, Dunant A et al (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 128:35–44PubMedCrossRef
2.
Zurück zum Zitat Mockenhaupt M (2005) Severe cutaneous adverse drug reactions. Clinical features and epidemiology. Hautarzt 56:24–31PubMedCrossRef Mockenhaupt M (2005) Severe cutaneous adverse drug reactions. Clinical features and epidemiology. Hautarzt 56:24–31PubMedCrossRef
3.
Zurück zum Zitat Tennis P, Stern RS (1997) Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 49:542–546PubMedCrossRef Tennis P, Stern RS (1997) Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 49:542–546PubMedCrossRef
4.
5.
Zurück zum Zitat Chang CC, Too CL, Murad S, Hussein SH (2011) 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 50:221–224PubMedCrossRef Chang CC, Too CL, Murad S, Hussein SH (2011) 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 50:221–224PubMedCrossRef
6.
Zurück zum Zitat Zhang Y, Wang J, Zhao LM et al (2011) 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 Zhang Y, Wang J, Zhao LM et al (2011) 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
7.
Zurück zum Zitat Man CB, Kwan P, Baum L et al (2007) Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 48:1015–1018PubMedCrossRef Man CB, Kwan P, Baum L et al (2007) Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 48:1015–1018PubMedCrossRef
8.
Zurück zum Zitat Wu XT, Hu FY, An DM et al (2010) Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epilepsy Behav 19:405–408PubMedCrossRef Wu XT, Hu FY, An DM et al (2010) Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epilepsy Behav 19:405–408PubMedCrossRef
9.
Zurück zum Zitat Lonjou C, Thomas L, Borot N et al (2006) A marker for Stevens-Johnson syndrome…: ethnicity matters. Pharmacogenomics J 6:265–268PubMed Lonjou C, Thomas L, Borot N et al (2006) A marker for Stevens-Johnson syndrome…: ethnicity matters. Pharmacogenomics J 6:265–268PubMed
10.
Zurück zum Zitat Alfirevic A, Jorgensen AL, Williamson PR et al (2006) HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics 7:813–818PubMedCrossRef Alfirevic A, Jorgensen AL, Williamson PR et al (2006) HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics 7:813–818PubMedCrossRef
11.
Zurück zum Zitat Kazeem GR, Cox C, Aponte J et al (2009) High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenet Genomics 19:661–665PubMedCrossRef Kazeem GR, Cox C, Aponte J et al (2009) High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenet Genomics 19:661–665PubMedCrossRef
12.
Zurück zum Zitat Gogtay NJ, Bavdekar SB, Kshirsagar NA (2005) Anticonvulsant hypersensitivity syndrome: a review. Expert Opin Drug Saf 4:571–581PubMedCrossRef Gogtay NJ, Bavdekar SB, Kshirsagar NA (2005) Anticonvulsant hypersensitivity syndrome: a review. Expert Opin Drug Saf 4:571–581PubMedCrossRef
13.
Zurück zum Zitat Chung WH, Hung SI, Hong HS et al (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428:486PubMedCrossRef Chung WH, Hung SI, Hong HS et al (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428:486PubMedCrossRef
14.
Zurück zum Zitat Lonjou C, Borot N, Sekula P et al (2008) European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18:99–107PubMedCrossRef Lonjou C, Borot N, Sekula P et al (2008) European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18:99–107PubMedCrossRef
15.
Zurück zum Zitat McCormack M, Alfirevic A, Bourgeois S et al (2011) HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364:1134–1143PubMedCrossRef McCormack M, Alfirevic A, Bourgeois S et al (2011) HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364:1134–1143PubMedCrossRef
16.
Zurück zum Zitat Ferrell PB Jr, McLeod HL (2008) Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 9:1543–1546PubMedCrossRef Ferrell PB Jr, McLeod HL (2008) Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 9:1543–1546PubMedCrossRef
Metadaten
Titel
The association between AED-induced cutaneous adverse drug reactions and the HLA-A, -B, and -DRB1 alleles among Caucasian patients: a pilot multicenter study
verfasst von
X. Wu
W. Graf
F.C. Schmitt
G. Kurlemann
W.S. Kunz
M. Heers
B. Kasper
H. Hamer
D. Zhou
Prof. H. Stefan
Publikationsdatum
01.11.2012
Verlag
Springer-Verlag
Erschienen in
Clinical Epileptology / Ausgabe 4/2012
Print ISSN: 2948-104X
Elektronische ISSN: 2948-1058
DOI
https://doi.org/10.1007/s10309-012-0268-0

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