Abstracts

Pharmacogenetics is the study of genetic influences on the response to drug treatment and is pertinent to disorders such as epilepsy in which more than 30% of patients fail to respond to current medications. We have commenced a pharmacogenetic investigation in a cohort of epilepsy patients attending our tertiary referral centre. Four hundred epilepsy patients have been included in the study to date (118 idiopathic generalised, 270 localisation related, 12 unclassified). Genomic DNA was extracted from venous blood and single nucleotide polymorphisms (SNPs) investigated by PCR and restriction digest. Patients were categorised as responders (seizure free for at least 12 months) or non-responders by review of case notes and seizure diaries. Allele and genotype frequencies were compared by logistic regression analysis. A total of 170 (42%) patients were classified as responders and 230 (58%) as non-responders. The prevalence of recognised SNPs in the MDR1, SCN1A, SCN2A, GABBR1, IL1B, 5HTT and KCNJ10 genes was correlated with outcome. Only the R19K polymorphism in the SCN2A gene showed a significant association with response to treatment, with variant genotypes present in 8% of responders and 16% of non-responders (odds ratio 2.07, 95% CI 1.08-3.97, p=0.024). All other analyses were without significant findings. Performing random studies of single SNPs in small cohorts of adult epilepsy patients appears to be of limited value in predicting response to drug treatment. More focused, large-scale investigations of variations across entire genes in less heterogeneous populations of patients may be required before the pharmacogenetics of epilepsy can be unravelled. In this regard, collaborative research efforts might hold the key. (Supported by grant awards to GJS from GI / Hall funds, University of Glasgow and West Research Endowment Funds, North Glasgow University Hospitals NHS Trust.)