• Pharmacogenet. Genomics · Sep 2009

    Comparative Study

    High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients.

    • Gbenga R Kazeem, Charles Cox, Jennifer Aponte, John Messenheimer, Celia Brazell, Andrew C Nelsen, Matthew R Nelson, and Elizabeth Foot.
    • GlaxoSmithKline, Harlow, UK. gbenga.r.kazeem@gsk.com
    • Pharmacogenet. Genomics. 2009 Sep 1;19(9):661-5.

    BackgroundSevere cutaneous adverse reactions (SCARs) are associated with over 200 medicines including lamotrigine, an antiepileptic drug. Previous studies have suggested the involvement of immune mechanisms in the development of drug-induced SCARs.MethodsHigh-resolution HLA genotyping was performed for 65 patients of European ancestry treated with lamotrigine (22 cases with lamotrigine-induced SCARs and 43 controls on lamotrigine without SCAR-related symptoms). Association of HLA genetic variants with SCARs in these patients were evaluated by contrasting allele frequencies between the cases and the controls for each of 112 HLA four-digit alleles.ResultsFive alleles were observed with higher frequencies in the cases compared with the treated controls with exact P values less than 0.05. These include B*5801 (P = 0.037), previously reported to be associated with allopurinol-induced SCARs. Marginal association evidence was also observed for alleles Cw*0718 and DQB1*0609, both of which were strongly correlated with B*5801. Other alleles identified were A*6801 (P = 0.012) and DRB1*1301 (P = 0.045). In contrast to the study of carbamazepine-induced Stevens-Johnson syndrome in Han Chinese patients, none of the cases carried B*1502. Accounting for the large number of hypothesis tests conducted, none of the associations identified were statistically significant.ConclusionNo single major HLA-related genetic risk factor was identified for lamotrigine-induced SCARs in patients of European origin. Only suggestive evidence was obtained for B*5801, A*6801, Cw*0718, DQB1*0609, and DRB1*1301. Confirmation of these results in a larger, independent sample is needed to determine whether any of the HLA alleles identified are truly associated with the development of lamotrigine-induced SCARs.

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