Abstracts

We identified a polymorphism in the potassium ion channel gene KIR4.1 (KCNJ10) that demonstrates suggestive evidence for association with human seizure disorder. KIR4.1 was chosen for study based on linkage data from a mouse multi-gene model of seizure susceptibility. The polymorphism causes an amino acid substitution in KIR4.1 (C1037T, R271C) and was tested for association with common types of epilepsy using a case-control study design. Allele frequency in epilepsy patients (n = 178) was compared to matched (age, sex, ethnicity) controls (n = 138) to determine if the polymorphism is associated with illness. We examined DNA from patients with focal temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) including; juvenile myoclonic, juvenile absence and childhood absence. When all ill individuals were combined for analysis, the frequency of the T allele was significantly greater in controls (0.102) compared to patients (0.053, ?2p < 0.036). When epilepsy subtypes were analyzed, the unequal allele distribution was no longer statistically significant, p < 0.089 for IGE (n=138) and p < 0.120 for TLE (n=40), possibly due to the smaller sample size. Although a p value of < 0.036 shows that the allele distribution is different between combined ill and control populations, statistical significance of association with illness can only be validated by confirmation in a separate population or through a family based transmission study. These data suggest that this polymorphism may represent a protective allele against seizure susceptibility in multiple epilepsy phenotypes.