Abstracts

Rationale: Epilepsy is one of the most common disorders of the brain. One of every ten people will have at least one epileptic seizure during a normal lifespan, and a third of these will develop epilepsy. Medical treatment with one or more antiepileptic drugs (AEDs) will render a majority of patient seizure free. However, despite long term treatment with various AEDs, about 30% of patients with epilepsy remain medically intractable. Recently, several genetic factors have been found to be associated with the occurrence of refractory epilepsy. The discovery of CNVs has had far-reaching implications for disease research, enabling scientists to correlate genetic alterations with disease. For epilepsy, altered CNV has been found to be related to the different types of seizure disorders. Furthermore, evolving data showed that CNV may also play an important role in pathogenesis of epilepsy. Though we have accumulating data showing that seizure patterns of epilepsy, the occurrence of RE are associated with different level of genetic variations, CNV has not yet been well explored for describing the mechanisms of RE occurrence. CNVs, as inter-individual significant minor variants, should be good candidates for the association study between phenotypes and genotypes in RE. Methods: This project will be a three-year prospective observational study in a naturalistic out-patient clinical setting. In total, 200 epilepsy patients (100 drug resistance epilepsy patients and 100 drug responsive epilepsy patients) will be recruited. They will be assigned into different groups throughout the study according to their clinical manifestation and the responsiveness of AEDs. The copy number variations in the whole genome of each individual will be determined by using the DNA microarray copy number variation analysis. ANOVA and chi-square test will be used for testing the association between the copy number variations and the occurrence of refractory epilepsy. Meanwhile, multivariate logistic regression model will be performed for analyzing the strength of association between those genetic factors and the disease progression after adjustment of the covariates. Results: Totally 405 patients were recruited in our study. The mean age of all our patients were 42.9 year (SD 15.336); 244 (60.2%) were male, and 161 (39.8%) were female. Frou our finding, we have found 9 loci upon the whole human genome, related to the occurence of RE. The result has been summarized in the table. Conclusions: From our result, we will understand the impact of the copy number variations and its magnitude on the occurrence of refractory epilepsy. Our results will not only provide the information of basic research about the influence of genomic structural variations and gene-environment interaction on the RE, but also set up a foundation for future research on the epidemiological and genetic study of RE in our Taiwanese population.