The Differential Manifestation of Alcohol Withdrawal Symptoms Related to GABAAalpha6 Polymorphism

Han, Doug Hyun; Choi, Jung Eun; Lee, Byung Young; Kim, Young Hoon; Kim, Hae Won; Lee, Hye Kyung

Abstract

INTRODUTION: The gamma-aminobutyric acid type A (GABAA) receptor is an important pharmacological target of alcohol. The phamacological characteristics of the receptor are largely determined by its subunit composition. Compared with all other alpha subtypes, the alpha6- containing receptors are more sensitive to GABA and less sensitive to benzodiazepines. The purpose of this study was to address a role for GABAAalpha6 receptor subunit gene in the development of alcohol dependence. The differential manifestation of alcohol withdrawal symptoms related to GABAAalpha6 polymorphism in patients treating with benzodiazepines was also examined.
METHODS
Eighty-seven inpatients with alcohol dependence, and sixty healthy controls were evaluated using CIWA-Ar scale. Each patient was genotyped for GABAAalpha6 subunit. Association between GABAAalpha6 polymorphism and severity of withdrawal symptom were determined.
RESULTS
No significant difference was found in GABAAalpha6 receptor genetic type and allelic distribution between the alcohol dependent and control subject. Tremor was more severe in CC than TT type. TT type had higher degree of anxiety, agitation and headache than CC type. The GABAAalpha6 C allele increased the average score of tremor significantly, and T allele increased that of agitation.
CONCLUSION
The results suggested that GABAAalpha6 genetic polymorphism was not associated with alcohol dependence and with severity of alcohol withdrawal symptoms. But in benzodiazepine treated patients, GABAAalpha6 polymorphism and allelic type show the difference in severity of each withdrawal symptom. These differences of severity are partly responsible for the unique pharmacological properties associated with the GABAAalpha6 subunit.