Abstracts

A previous report in a Austrian population identified positive association between a variation in the promoter of the prodynorphin gene (PDYN) and risk for acquiring temporal lobe epilepsy (TLE). This association was seen in TLE patients that had a family history of epilepsy (at least one first or second degree relative with epilepsy) but not in TLE patients without a family history. The variation affects promoter activity in an [italic]in vitro[/italic] assay and is a plausible candidate for an epilepsy susceptibility gene. However, a subsequent study in a separate German population found no association between the PDYN polymorphism and TLE with familial history. We replicated these studies with twice the number of patient samples compared to the previous reports.
All patients were recruited in Philadelphia, PA, USA, and provided signed informed consents for these studies. DNA was obtained after extraction from a peripheral blood sample. The variation is a 68bp repeat element that occurs in human populations in one, two, three or four copies of the repeat per allele. PCR was used to amplify the region surrounding the repeat element and genotypes were visualized on 5% non-denaturing polyacrylamide gels with ethidium bromide staining. Gels were photographed and scored by two independent readers. Genotypes and allele frequencies were analyzed by Chi square contingency analysis.
Genotypes from a total of 158 TLE patients of European ancestry (74 with a positive family history) and 143 controls were analyzed. Alleles with one or two copies of the repeat were designated as [ldquo]low[rdquo] whereas alleles with three or four copies of the repeat were designated as [ldquo]high[rdquo]. All genotypes were in Hardy-Weinberg equilibrium. We found no significant difference in genotype distribution or in allele frequency between the TLE patients and controls. Frequency of the high and low alleles in controls was 67% and 33% respectively, in TLE patients it was 66% and 34% respectively. There was no significant difference in allele frequency between those TLE patients with and without a positive family history. High and low alleles frequencies were 68% and 32% in TLE without family history of epilepsy (n=84) and 65% and 35% in TLE patients with a family history of epilepsy (n=74).
Our results suggest that the PDYN promoter variation under study is not associated with the phenotype of temporal lobe epilepsy in this patient population. It is possible that the discrepancy between our data and those published previously may be explained, in part, by increased genetic heterogeneity of the US population compared to those studied in Europe.
[Supported by: NIH RO1NS-40396 to RJB and The University of Pennsylvania Center for Neurobiology and Behavior.]