Severe 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.
High-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.
RESULTS:
Five alleles were observed with higher frequencies in the cases compared with the treated controls with exact P values less than 0.05.
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.
CONCLUSION:
No 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.
"High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients."
Pharmacogenet Genomics. 2009 Aug 6; Kazeem GR, Cox C, Aponte J, Messenheimer J, Brazell C, Nelsen AC, Nelson MR, Foot E
Related:
High-resolution HLA genotyping and severe cutaneous adverse
Cutaneous Adverse Reactions: Stevens-Johnson Syndrome
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High-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.
RESULTS:
Five alleles were observed with higher frequencies in the cases compared with the treated controls with exact P values less than 0.05.
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.
CONCLUSION:
No 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.
"High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients."
Pharmacogenet Genomics. 2009 Aug 6; Kazeem GR, Cox C, Aponte J, Messenheimer J, Brazell C, Nelsen AC, Nelson MR, Foot E
Related:
High-resolution HLA genotyping and severe cutaneous adverse
Cutaneous Adverse Reactions: Stevens-Johnson Syndrome
Review: severe cutaneous adverse reactions to drugs
In the pursuit of classifying severe cutaneous adverse reactions
Cutaneous adverse reactions to valdecoxib distinct from stevens ...
Study: cutaneous adverse reactions to valdecoxib distinct from ...
