HLA-A*11:01 is associated with levetiracetam-induced psychiatric adverse events

Tae-Won Yang, Jangsup Moon, Tae-Joon Kim, Jin-Sun Jun, Jung-Ah Lim, Soon-Tae Lee, Keun-Hwa Jung, Kyung-Il Park, Ki-Young Jung, Kon Chu, Sang Kun Lee, Tae-Won Yang, Jangsup Moon, Tae-Joon Kim, Jin-Sun Jun, Jung-Ah Lim, Soon-Tae Lee, Keun-Hwa Jung, Kyung-Il Park, Ki-Young Jung, Kon Chu, Sang Kun Lee

Abstract

Levetiracetam (LEV) is effective for focal and generalized epilepsy and is used worldwide because of its relatively few drug interactions and favorable tolerability. However, some psychiatric adverse events (PAEs) have been reported, resulting in drug withdrawal. The pathophysiology of LEV-induced PAE has not yet been elucidated. In this study, we investigated the relationship between PAEs and human leukocyte antigen (HLA) genes. Eleven epilepsy patients, who developed PAEs after the administration of LEV and spontaneously improved after drug withdrawal, were enrolled retrospectively. Genomic DNA from the peripheral blood was extracted, and four-digit allele genotyping of HLA genes was performed. The genotype frequencies of HLA genes were compared to those of 80 patients in which LEV was well tolerated, as well as to 485 individuals from the general Korean population. The frequency of the HLA-A*1101 allele was significantly higher in the LEV-induced PAEs group compared to both the LEV-tolerant group (p = 0.021, OR 4.80, 95% CI 1.30-17.74) and the general Korean population (p = 0.015, OR 4.62, 95% CI 1.38-15.45). This study is the first attempt at investigating the relationship between the HLA system and LEV-induced PAE. The results of this study suggest that the HLA-A*1101 allele could be a risk factor for the development of PAEs.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. In-silico modeling of the molecular…
Fig 1. In-silico modeling of the molecular interaction between HLA-A*1101 and LEV.
The LEV molecule was predicted to be docked into the P1 pocket of HLA-A*1101 with relatively higher affinity (5.1 kcal/mol) compared to other HLA-A subtypes. HLA, human leukocyte antigen; LEV, levetiracetam.

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