EXPRESSION PROFILING AND IDENTIFICATION OF SLC2A1 AS A CANDIDATE GENE FOR VARIABLE RESPONSE OF KETOGENIC THERAPY IN UNCONTROLLED EPILEPSY PATIENTS

Abstract

Uncontrolled epilepsy is one such condition, which leads to recurrent seizures even after two to three trails of anti-epileptic drugs. Ketogenic diet has been validated as an effective treatment for uncontrolled epilepsy. Ketodiet helps in reduction of seizures and overall improvement of health of the patients. Inspite of all these, keto diet shows variable response rate in the patients. The variable response might be due to variable genetic makeup of the individual patients. The present study investigates the effect of the ketogenic diet through gene expression profiling using blood samples and qPCR techniques. 51 uncontrolled epilepsy patients and 50 healthy controls were included in this study, blood samples were collected in PAXgene tubes followed by RNA isolation from PAXgene blood RNA kit, cDNA conversion using Thermoscientific cDNA Reverse Transcription Kit, and qPCR using Maxima SYBR® Green qPCR master mix. The fold changes of gene expression was calculated using formula 2^- (ΔΔ Ct) Statistical analysis was done through Welch's t-test. Relative to controls (n=50), SLC2A1 expression was reduced to 0.382-fold in patients achieving complete seizure freedom (100% SRR, n=18), 0.111-fold in patients with ≥90% seizure reduction (90% SRR, n=12), 0.009-fold in patients with >50% seizure reduction (n=8), and 0.003-fold in patients with poor treatment response (<50% SRR, n=13), all reaching high statistical significance (p < 0.0001). These findings support SLC2A1 as a novel candidate biomarker for epilepsy treatment stratification. They further provide a molecular basis for evaluating ketogenic dietary therapy in SRR-defined, treatment resistant patient subgroups....