Relationship between a GABA(A)alpha 6 Pro385Ser substitution and benzodiazepine sensitivity

Objective: In humans, interindividual variation in sensitivity to benzodiaz epine drugs may correlate with behavioral variation, including vulnerabilit y to disease states such as alcoholism. In the rat, variation in alcohol an d benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)alpha 6 receptor. The authors detected a Pro385Ser [1236C>T] amino acid substitution in the human GABA(A)alpha 6 that may influence alco hol sensitivity. In this pilot study, they evaluated the contribution of th is polymorphism to benzodiazepine sensitivity. Method: Sensitivity to diaze pam was assessed in 51 children of alcoholics by using two eye movement mea sures: peak saccadic velocity and average smooth pursuit gain. Association analysis was performed with saccadic velocity and smooth pursuit gain as de pendent variables and comparing Pro385/Ser385 heterozygotes and Pro385/Pro3 85 homozygotes. Results: The Pro385Ser genotype was associated with less di azepam-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 wit h this trait.