| pA2 online © Copyright 2004 The British Pharmacological Society |
174P
University of Newcastle Winter Meeting December 2004 |
Lack of association between serious carbamazepine hypersensitivity reactions and HLA-B in caucasians Ana Alfirevic1, David W. Chadwick2, B. Kevin Park1 & Munir Pirmohamed1. 1Department of Pharmacology & Therapeutics, The University of Liverpool, Sherrington Building, Ashton Street, Liverpool, 2Department of Neurological Sciences, Walton Centre for Neurology and Neurosurgery, The University of Liverpool, Long Lane, Liverpool. |
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Print abstractThe use of carbamazepine (CBZ), the most commonly prescribed antiepileptic drug, is hampered by the occurrence of severe, potentially lethal hypersensitivity reactions. The pathogenesis of hypersensitivity is unclear, although predisposition to CBZ hypersensitivity is genetically determined. Recently, a strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome was reported in Han Chinese patients [1] with all affected patients possessing the allele. We have previously shown an association between serious CBZ hypersensitivity reaction and the ancestral haplotype 8.1 on the major histocompatibility complex, which is not in linkage disequilibrium with HLA-B*1502 [2]. We have therefore undertaken HLA-B genotyping to determine whether there is an association with CBZ hypersensitivity in Caucasian patients.
We included 20 Caucasian patients with serious CBZ-induced reactions (17 with hypersensitivity syndrome and 2 with Stevens-Johnson syndrome), 39 patients with mild skin rashes due to CBZ intake and 43 control patients on CBZ without adverse effects. HLA-B genotyping was done by Anthony Nolan Trust Histocompatibility Laboratories (London, UK) using PCR-SSO (sequence specific oligonucleotide probes) methodology. Ethics committee approval was obtained. By contrast to the finding of Chung et al. [1] in Chinese patients, none of our patients was positive for HLA-B*1502. We found that HLA-B*0702 was absent in our group with serious hypersensitivity reactions, but present at frequencies of 17.4% and 14.6% in the control group and patients with mild reactions, respectively. However, correction for the multiple testing (30 alleles) resulted in a non-significant finding.Our data suggest that HLA-B*1502 is not a predisposing factor for CBZ-induced hypersensitivity in Caucasians. Furthermore, the absence of HLA-B*1502 in two of our patients with Stevens-Johnson syndrome indicates that it may not be as strong a genetic marker in Caucasians as has been demonstrated in Han Chinese, but clearly this needs to be evaluated in a larger Caucasian cohort.
1. Chung W-H, et al. Nature 2004; 428: 486.
2. Pirmohamed M, et al. Neurology 2001; 56: 890.