Abstracts

ASSOCIATION ANALYSIS BETWEEN A FUNCTIONAL POLYMORPHISM IN THE PRODYNORPHIN GENE PROMOTER AND DIFFERENT TYPES OF SEIZURE DISORDERS

Abstract number : 3.079
Submission category :
Year : 2002
Submission ID : 449
Source : www.aesnet.org
Presentation date : 12/7/2002 12:00:00 AM
Published date : Dec 1, 2002, 06:00 AM

Authors :
Nikola Tilgen, Johannes Rebstock, Christian E. Elger, Thomas Sander, Armin Heils. Institute of Human Genetics, University of Bonn, Bonn, Germany; Clinic of Epileptology, University of Bonn, Bonn, Germany; Clinic of Neurology, University Clinic Charite, Be

RATIONALE: Several studies have established the prodynorphin gene (PDYN) as a prime candidate gene for increased seizure susceptibility. A common functional polymorphism has been identified in the PDYN gene promoter with [dsquote]low-expression-alleles[dsquote] (L) consisting of either 1 or 2 repetitive 68bp elements, and [dsquote]high-expression-alleles[dsquote] (H) consisting of 3 or 4 repeat elements, respectively. Recently, L-alleles have been shown to be associated with an increased risk for temporal lobe epilepsy in patients with a family history for seizures (Stoegmann et al., 2002).
METHODS: In our study we first attempted to confirm the latter findings by genotyping the PDYN polyorphism in 160 TLE patients, of which 43 patients reported a family history of seizures. Second, we extended our study sample by investigating 104 patients with febrile seizures (FS) and 275 probands with idiopathic generalized epilepsy (IGE). In the FS group, a family history of seizures was reported in 45 cases and in 106 probands of the IGE group, respectively.
RESULTS: First, we found a trend towards the same allelic distribution as described by Stoegmann et al., although our results did not reach a significance level of p[lt].05. However, we found a significant association between the L-alleles and an increased risk for FS in patients with a positive family history for seizures. Within the IGE study sample we detected only a trend towards a susceptibility effect of the L-alleles, however, when we split the entire IGE sample into the main diagnostic subgroups, we found a significant effect in patients with idiopathic absence epilepsy who were derived from families with at least one affected sibling.
CONCLUSIONS: Our results show that the L-alleles of the PDYN gene promoter may probably be regarded as a general seizure susceptibilty factor for different types of seizure disorders. Further studies are required to confirm these findings and may thus open new research avenues for the development of target-directed antiepileptic compounds.
Reference: Stoegman et al. (2002) A functional polymorphism in the prodynorphin gene promoter is associated with temporal lobe epilepsy. Ann Neurol 51, 260-263
[Supported by: The Deutsche Forschungsgemeinschaft (DFG)]