The 1674+11C>T polymorphism of CHRNA4 is associated with juvenile myoclonic epilepsy.

The alpha4 subunit gene (CHRNA4) of the neuronal nicotinic acetylcholine receptor (nAChR), linked to an idiopathic partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), may also play a key role in the development of the idiopathic generalized epilepsy syndrome (IGE), juvenile myoclonic epilepsy (JME). This study was designed to explore an association of four polymorphisms of the CHRNA4 with JME in Polish children and young patients. The study included 92 JME patients and 222 unrelated healthy individuals. In each group the frequencies of the CHRNA4 c.555C>T, c.594C>T, 1674(+11)C>T, and 1674(+14)A>G polymorphisms were determined using PCR-RFLP analyses. An association between the 1674(+11)C>T polymorphism of the CHRNA4 and JME was evidenced. Allele T (the risk factor) appeared with a significantly higher frequency in the JME patients than in the controls (p=0.0299). The patients harboring the 1674(+11)CT+TT genotypes showed an increased risk of JME (CT+TT versus CC: OR=1.925; 95% CI=1.021-3.629; p=0.0408). No association was found for the other CHRNA4 polymorphisms tested. The CHRNA4 1674(+11)C>T polymorphism may be a susceptibility factor for epilepsy, and its higher frequency in patients with juvenile myoclonic epilepsy suggests that the CHRNA4 may be one of the candidate genes for this epileptic syndrome.