Relationship between a GABAA alpha 6 Pro385Ser substitution and benzodiazepine sensitivity.
OBJECTIVE
In humans, interindividual variation in sensitivity to benzodiazepine drugs may correlate with behavioral variation, including vulnerability to disease states such as alcoholism. In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABAA alpha 6 receptor. The authors detected a Pro385Ser [1236C > T] amino acid substitution in the human GABAA alpha 6 that may influence alcohol sensitivity. In this pilot study, they evaluated the contribution of this polymorphism to benzodiazepine sensitivity.


METHODS
Sensitivity to diazepam was assessed in 51 children of alcoholics by using two eye movement measures: peak saccadic velocity and average smooth pursuit gain. Association analysis was performed with saccadic velocity and smooth pursuit gain as dependent variables and comparing Pro385/Ser385 heterozygotes and Pro385/Pro385 homozygotes.


RESULTS
The Pro385Ser genotype was associated with less diazepam-induced impairment of saccadic velocity but not with smooth pursuit gain.


CONCLUSIONS
The Pro385Ser genotype may play a role in benzodiazepine sensitivity and conditions, such as alcoholism, that may be correlated with this trait.
Iwata
N
N
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., USA. nakao@fujita-hu.ac.jp
Cowley
D S
DS
Radel
M
M
Roy-Byrne
P P
PP
Goldman
D
D
D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D016241:Child of Impaired Parents; D003975:Diazepam / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011698:Pursuit, Smooth / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics*; D012438:Saccades / Q000187:drug effects / Q000235:genetics; D012694:Serine / Q000235:genetics
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D012694:Serine; D011392:Proline; D003975:Diazepam