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CYP2C variants associated with severe phenytoin-related cutaneous reactions
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Researchers have identified CYP2C variants, including CYP2C9*3, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.
A case control study included 105 cases with phenytoin-related severe cutaneous adverse reactions, 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants and 3,655 population controls from Taiwan, Japan and Malaysia.
Researchers also completed a genome-wide association study of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan.
Through the genome-wide association study, the researchers discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance.
Direct sequencing of the genes resulted in the identification of missense variant rs1057910 (CYP2C9*3), which showed a significant association with phenytoin-related severe cutaneous adverse reactions, according to the researchers.
A meta-analysis of the cases from Taiwan, Japan and Malaysia also demonstrated a statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions, with an overall odds ratio of 11.
Patients who had severe cutaneous adverse reactions, particularly CYP2C9*3 carriers, were detected to have a delayed clearance of plasma phenytoin, which provided a functional link between the associated variants and the disease, according to the researchers.
Disclosure: Chung and Hung have a patent application pending for risk assessment for phenytoin-induced adverse drug reactions.
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