The G protein ß3 subunit polymorphism may modify the presentation of temporal lobe epilepsy.

ABSTRACT Purpose: Experimental studies suggest a role of G protein-mediated signaling pathways in epileptogenesis. A genetic variation in the G protein subunit Gâ3 denoted the C825T polymorphism has been reported to increase the signaling efficiency through Gi proteins and to modify responses to certain drugs. The C825T polymorphism has also been associated with several diseases including hypertension, diabetes type II and obesity and major depressive disorder. In the present study we have explored whether the G protein polymorphism C825T is associated with or influences temporal lobe epilepsy (TLE). Methods: The study included 227 TLE patients, 186 controls and 106 family members of TLE patients. DNA was extracted from blood samples, and typing of the polymorphism was performed. Case record forms were analyzed for all the homozygote TLE-patients and homozygote controls as well as for 28 matched TLE-patients without the mutation (16 females, 12 males). Results: Typing of the C825T polymorphism showed that 6% of the TLE patients, 7% of the controls and 7,5% of the family members were homozygote for the polymorphism; i.e. carrying the TT genotype. There were, however, differences between the homozygote TLE patients and the TLE patients without the polymorphism with regard to the phenotype. The TLE patients carrying the TT genotype had a higher severity score on 8 of 9 pre-defined parameters. In agreement with other studies, the TT genotype TLE patients also had increased body mass index, weight and waist circumference compared to the TLE patients without the polymorphism; i.e. carrying the CC genotype, but there was no higher frequency of hypertension or diabetes. Conclusions: There was no increased frequency of TLE between the carriers of the TT genotype compared to healthy controls and/or family members without epilepsy. However, the TLE patients with the TT genotype showed tendencies of a more severe disease phenotype