Polymorphism of the long polyglutamine tract in the human androgen receptor influences craving of men in alcohol withdrawal

Abstract

Until recently, genetic mechanisms influencing craving in alcohol withdrawal were poorly understood. Studies show that alcoholism is associated with dysregulation of sexual hormones. The androgen receptor is encoded by the trinucleotide repeat CAG. Long repeat regions have been shown to inhibit interactions between the androgen receptor and different co-activators. The aim of the present study was to determine whether or not this trinucleotide repeat is involved in the pathogenesis of alcohol dependence, withdrawal and craving. We included 112 male inpatients who were admitted for detoxification treatment. To measure the extent of craving we used the Obsessive Compulsive Drinking Scale on the day of hospital admission. Regarding total and obsessive craving we found a significant negative correlation for the androgen receptor repeat length. No significant difference between the group of patients and the control group was found. We found that reduced length of the investigated trinucleotide repeat might aggravate craving symptoms. Moreover, an elevated number of repeats might be protective against severe craving. In summary, the presented data points to an underestimated role of the genetic regulation of androgens in the pathogenesis of alcohol dependence and related disorders.