The role of pharmacogenetics of cytochrome P450s in phenytoin-induced DRESS syndrome

细胞色素P450的药理遗传学在苯妥英钠诱导的药物反应伴嗜酸性粒细胞增多和全身症状综合征中的作用

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Abstract

Anil et al. (2017) report a patient who presented with drug rash with eosinophilia and systemic symptom (DRESS) syndrome. It may be induced by various drugs. In the mentioned report DRESS syndrome has been attributed to phenytoin use. CYP2C9 is a genetically polymorphic enzyme, and decreased metabolism of many drugs has been reported in the subjects carrying variants of rs1799853 and rs1057910, which were designated as CYP2C9*2 and *3. rs3758581, the variant investigated by Anil et al., is a genetic variant of CYP2C19 (not that of CYP2C9, as stated and discussed in the report). CYP2C19 is also a highly genetically polymorphic enzyme, and rs3758581 may be present in 40 different haplotypes of CYP2C19 including *2 and *17 (for detailed information: www.pharmvar.org/gene/CYP2C19). Detection of rs3758581 is not sufficient because the patient presented by Anil H et al. may have CYP2C19*2, CYP2C19*17, or any other variant due to the co-appearance of other possible genetic variations. It is of importance to perform the correct genetic analysis because CYP2C19*2 is associated with low enzyme activity but CYP2C19*17 is associated with increased enzyme activity. CYP2C9 is a major enzyme responsible for the metabolism of phenytoin. CYP2C9*2 (rs1799853) and *3 (rs1057910) should be considered in a Caucasian subject. CYP2C19 (especially *2 and *17) and ABCB1 polymorphisms may also be considered for the evaluation of the patient. Additionally, serum phenytoin levels would be helpful to understand the contribution of genetic polymorphisms on the pharmacokinetics of phenytoin in the patients presenting side effects like DRESS syndrome.

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