Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transportingATPase

Genetic linkage studies in rodents and humans have identified specific chro mosomal regions harboring seizure susceptibility genes, We have identified a novel polymorphism in the human alpha 2 subunit gene (ATP1A2) of the sodi um potassium transporting ATPase (NaK-pump), a candidate gene for human tem poral lobe epilepsy (TLE) based on its chromosomal location and function in ion homeostasis. The polymorphism consists of a four base pair insertion 1 2 base pairs upstream of the start of exon 2, We performed an association s tudy between this polymorphism and TLE, Our study did not find a significan t difference in the frequency of this polymorphism between TLE patients and controls, indicating that this variation is not a major susceptibility fac tor. However, since the number of patients studied so far is small and the functional consequence of the polymorphism is unknown, the variation may ye t be found to play a minor role in increased risk for seizure susceptibilit y, In contrast to the findings in TLE patients and controls, we did find a significant difference in the frequency of the variation between African Am ericans and persons of European descent. This finding demonstrates the pote ntial effect of population stratification on studies of this type and suppo rts the growing use of parental and familial samples for controls in associ ation studies. Further study of this polymorphism is warranted as it may be involved in other disease processes for which there are known ethnic-speci fic susceptibilities. Am, J, Med. Genet. (Neuropsychiatr, Genet.) 96:79-83, 2000, (C) 2000 Wiley-Liss, Inc.