Genetic Variations of ABCC2 Gene Associated with Adverse Drug Reactions to Valproic Acid in Korean Epileptic Patients

다국어 초록 (Multilingual Abstract)

The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions(ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Ourobjective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. Weexamined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adversereactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimatedby logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the mostfrequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%,p = 0.0057) and the GG genotype (61.0% vs. 39.7%, p = 0.019) at the g.‒1774delG locus. The frequency of the haplotypecontaining g.‒1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p= 0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.‒1774delG locuswas identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). Wedemonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulnessof ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

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