Association analysis between a regulatory-promoter polymorphism of the human monoamine oxidase A gene and idiopathic generalized epilepsy

Monoaminergic neurotransmission plays an important role in the regulation o f neuronal network excitability and seizure activity. Therapeutic inhibitio n of the mitochondrial enzyme monoamine oxidase A (MAO-A), which is involve d in the degradation and inactivation of monoaminergic neurotransmitters, h as been shown to confer a potent anticonvulsant effect. These and other fin dings suggest a possible role of the X-linked MAO-A gene in epileptogenesis . Therefore, our study was designed to test for an association between a no vel MAO-A gene promoter polymorphism and common subtypes of idiopathic gene ralized epilepsy (IGE). The length of a 30-bp repetitive sequence similar t o 1.2 kb upstream of the ATG initiation codon was assessed in 126 patients with juvenile myoclonic epilepsy (JME), 122 patients with idiopathic absenc e epilepsy (IAE), and 248 healthy controls of German descent. Both sexes we re analyzed separately. Although we observed a trend towards a lower number of heterozygotes carrying the 3 and 4 copy alleles in female IAE patients (chi(2) = 3.813, df = 1, P = 0.053), allele frequencies did not deviate sig nificantly between patients and controls. Thus, our results do not provide evidence for a contribution of the functional MAO-A gene promoter polymorph ism to the pathogenesis of common IGE subtypes. (C) 2000 Elsevier Science B .V. All rights reserved.