title: Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase.
abstract: Genetic linkage studies in rodents and humans have identified specific chromosomal regions harboring seizure susceptibility genes. We have identified a novel polymorphism in the human alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase (NaK-pump), a candidate gene for human temporal lobe epilepsy (TLE) based on its chromosomal location and function in ion homeostasis. The polymorphism consists of a four base pair insertion 12 base pairs upstream of the start of exon 2. We performed an association study between this polymorphism and TLE. Our study did not find a significant difference in the frequency of this polymorphism between TLE patients and controls, indicating that this variation is not a major susceptibility factor. However, since the number of patients studied so far is small and the functional consequence of the polymorphism is unknown, the variation may yet be found to play a minor role in increased risk for seizure susceptibility. In contrast to the findings in TLE patients and controls, we did find a significant difference in the frequency of the variation between African Americans and persons of European descent. This finding demonstrates the potential effect of population stratification on studies of this type and supports the growing use of parental and familial samples for controls in association studies. Further study of this polymorphism is warranted as it may be involved in other disease processes for which there are known ethnic-specific susceptibilities. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:79-83, 2000.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. rjbuono@mail.med.upenn.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Buono
authors.forename: T N
authors.initials: TN
authors.lastname: Ferraro
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connor
authors.forename: M R
authors.initials: MR
authors.lastname: Sperling
authors.forename: M
authors.initials: M
authors.lastname: Abbey
authors.forename: E
authors.initials: E
authors.lastname: Finanger
authors.forename: F
authors.initials: F
authors.lastname: Lohoff
authors.forename: N
authors.initials: N
authors.lastname: Mulholland
authors.forename: W H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics; D017931:DNA Primers; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D011110:Polymorphism, Genetic; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D017931:DNA Primers; C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase