Gene expression analysis of drug transporters and biotransformation enzyme in patients with MTLE and FCD: A comparative study

Introduction: One of the many hypotheses proposed to explain pharmacoresistance in epilepsy is Drug Transporter Hypothesis which suggests that antiepileptic drugs fail to reach targets in sufficient concentration due to upregulation of ABC drug transporters and biotransformation enzymes at blood brain barrier. To validate this hypothesis, we analyse the alteration in expression levels of few of the drug transporters MRP1, MVP, BCRP, and drug metabolising enzyme UGT1A4, in resected brain tissues of the mesial temporal lobe epilepsy (MTLE) and focal cortical dysplasia (FCD) patients compared with non-epileptic controls.

Methodology: RNA extracted from resected brain specimens of MTLE, FCD patients and non-epileptic controls were analysed by semi quantitative One-step RT-PCR to look for differential gene expression. HPRT gene was used as a constitutive expression control for normalisation. Expression results were quantified by densitometric analysis and scattered plots were generated.

Results and conclusion: We observed a broad upregulation of all 4 genes investigated in this study in both MTLE and FCD tissues compared to controls. Fold change for BCRP was 1.25 for MTLE and 1.4 for FCD; For MRP1 it was 1.5 for MTLE and 2 for FCD; In case of MVP it was 1.4 for MTLE and 1.5 for FCD. For UGT1A4, MTLE value was 1.42 and 1.46 for FCD. The upregulation was comparatively higher in FCD as compared to MTLE group for all genes. Upregulation for BCRP, MRP1 and UGT1A4 were statistically significant for Control versus FCD groups (p < 0.05). Further studies on bigger cohort of patients are required to conclude these findings.