Profiles of Multidrug Resistance Protein-1 in the Peripheral Blood Mononuclear Cells of Patients with Refractory Epilepsy

by Jae-Jun Ban, Keun-Hwa Jung, Kon Chu, Soon-Tae Lee, Daejong Jeon, Kyung-Il Park, Hye-Jin Moon, Hyeyun Kim, Sunghun Kim, Sang Kun Lee, Jae-Kyu Roh

Background

About one third of patients with epilepsy become refractory to therapy despite receiving adequate medical treatment, possibly from multidrug resistance. P-glycoprotein, encoded by multidrug resistance protein-1 (MDR1) gene, at the blood brain barrier is considered as a major factor mediating drug efflux and contributing to resistance. Given that peripheral blood mononuclear cells (PBMNCs) express MDR1, we investigated a MDR1 status of PBMNCs in various subsets of epilepsy patients and demonstrated their association with clinical characteristics.

Methodology/Principal Findings

Clinical and MDR1 data were collected from 140 patients with epilepsy, 30 healthy volunteers, and 20 control patients taking anti-epileptic drugs. PBMNCs were isolated, and basal MDR1 levels and MDR1 conformational change levels were measured by flow cytometry. MDR1 profiles were analyzed according to various clinical parameters, including seizure frequency and number of medications used in epilepsy patients. Epilepsy patients had a higher basal MDR1 level than non-epilepsy groups (p<0.01). Among epilepsy patients, there is a tendency for higher seizure frequency group to have higher basal MDR1 level (p = 0.059). The MDR1 conformational change level was significantly higher in the high-medication-use group than the low-use group (p = 0.028). Basal MDR1 (OR = 1.16 [95% CI: 1.060–1.268]) and conformational change level (OR = 1.11 [95% CI: 1.02–1.20]) were independent predictors for seizure frequency and number of medications, respectively.

Conclusions/Significance

The MDR1 profile of PBMNCs is associated with seizure frequency and medication conditions in patients with epilepsy.

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Profiles of Multidrug Resistance Protein-1 in the Peripheral Blood Mononuclear Cells of Patients with Refractory Epilepsy
Syndicated from:PLoS ONE

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