G protein beta3 subunit C825T polymorphism modifies the presentation of temporal lobe epilepsy.
OBJECTIVE
Experimental studies suggest a role of G protein-mediated signaling pathways in epileptogenesis. A genetic variation affecting the G protein subunit Gbeta3 denoted the C825T polymorphism has been reported to increase the signaling efficiency through G(i) proteins and to modify responses to certain drugs. The C825T polymorphism has also been associated with several diseases including hypertension, diabetes type II, obesity, and major depressive disorder. In this 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, i.e., carrying the TT genotype as well as for 28 matched TLE patients (16 females, 12 males) without the polymorphism (CC genotype).


RESULTS
Typing of the C825T polymorphism showed that 6.0% of the TLE patients, 7.0% of the controls, and 7.5% of the family members were homozygote for the polymorphism; i.e., carrying the TT genotype. TLE patients carrying the TT genotype had higher severity score on eight out of nine predefined parameters compared with the TLE patients without polymorphism, i.e., carrying CC genotype. TT genotype TLE patients also had increased body mass index, body weight, and waist circumference compared with the TLE patients carrying the CC genotype. There was no increased frequency of hypertension or diabetes.


CONCLUSIONS
There was no increased frequency of TLE between the carriers of the TT genotype compared with the healthy controls and/or family members without epilepsy. However, the TLE patients with the TT genotype showed tendencies of a more severe disease phenotype.
Osberg
S
S
Department of Neurology, Division of Clinical Neuroscience, Rikshospitalet University Hospital, Oslo, Norway. silje.osberg@gmail.com
Melien
O
O
Taubøll
E
E
Gjerstad
L
L
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D016022:Case-Control Studies; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000927:Anticonvulsants; C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins