DOI: 10.1097/ftd.0000000000001517 ISSN: 0163-4356
KCNA3 Gene Polymorphism Affects the Efficacy and Plasma Concentration of Perampanel in Patients With Refractory Epilepsy
Ting Zhao, Hong-Jian Li, Hui-Lan Zhang, Jing Yu, Yan Sun, Lu-Hai Yu, Lu-Feng Cheng
Background:
Perampanel (PER) is the only third-generation anti-seizure medication targeting AMPA receptors, but its efficacy varies between patients. Whether
KCNA3
polymorphisms influence PER response in drug-resistant epilepsy remains unknown. This study aims to evaluate the impact of
KCNA3
rs2821557 polymorphisms on PER efficacy and plasma concentrations in patients with refractory epilepsy.
Methods:
Blood samples were collected from 119 patients who received PER for at least 3 weeks, in accordance with inclusion and exclusion criteria.
KCNA3
rs2821557 genotypes were identified using first-generation Sanger sequencing, and plasma PER concentrations were quantified by ultra-high-performance liquid chromatography to assess associations between the
KCNA3
rs2821557 gene polymorphism, PER efficacy, and plasma drug concentrations.
Results:
The therapeutic efficacy of PER in managing patients with refractory epilepsy was 65.55% (78/119). The proportion of patients with the
KCNA3
rs2821557 TT genotype was significantly greater in the effective group than the ineffective group. Plasma PER concentrations in patients with CT or TT genotypes were significantly lower than in those with the CC genotype, a pattern also observed in patients aged 4–14 years, female patients, patients with a body mass index ranging from 18.5 to 24.0 kg/m, and patients with disease duration exceeding 1 year.
Conclusions:
The
KCNA3
rs2821557 polymorphism is an important predictor of the therapeutic efficacy of PER in controlling epileptic seizures and a determinant of the attainment of therapeutic plasma PER concentrations.