Abstract for presentation at The Australian and New Zealand Association of Neurologists Annual Scientific Meeting 2007

Multidrug resistance (MDR) proteins may play a role in brain transport of AEDs, and genetic variations in these have been proposed to affect drug efficacy. A number of publications have examined the association between a specific polymorphism (3435 TT/CC) in the MDR1 gene and AED efficacy in patients with chronic epilepsy, with conflicting results2,3,4,5. Where the previous studies were limited by multiple confounders and retrospective clinical data, the current study examines the relationship of this polymorphism to seizure recurrence in three international prospective cohorts of patients newly treated for epilepsy.
Methods: Patients newly commenced on medication for epilepsy were prospectively enrolled into three cohorts. Data was collected on demographics, medication details, and seizure control after 12 months of follow-up. Relevant factors that may differ between the centres were examined, including the distribution of genotype frequencies, ethnicity, medication usage and seizure types. The distribution of the MDR1 3435 TT vs CC genotypes were compared between patients with and without recurrent unprovoked seizures.
Results: 525 newly treated patients have been enrolled in this collaboration (195 from Australia, 285 from Scotland, and 45 from Hong Kong). 33.5% had recurrent unprovoked seizures within two years of starting an AED. Comparison of sex was not statistically different across the international centres. Genotype frequencies and ethnicity were not statistically significant between the Scottish and Australian cohorts, but both were significantly different compared to the HK cohort, which is likely to be due to the variation in ethnicity. The nature of the medication usage and rates of responsiveness to medication differed significantly between the centres. There was no relationship between the 3435 MDR genotype and the rate of recurrence of unprovoked seizures.
Conclusions: These data suggest that MDR genotype does not have a strong role in determining the efficacy of a newly started AED in controlling seizures.