The T-allele of the GNB3 825C>T polymorphism is associated with increased intensity of opiate withdrawal

Abstract

The intensity of withdrawal in opiate dependence shows a high inter-individual variability. The 825C>T-polymorphism (rs5443) of the G protein beta3 (GNB3) subunit gene has a strong influence on clinical signs of sympathetic activity in cardiac research. This study was carried out in order to test the hypothesis that carriers of the T allele have an increased sympathetic activity in opiate withdrawal. Thirty-nine monovalent opiate addicted patients consecutively admitted to a detoxification ward were investigated. The main parameter for sympathetic activity was the pulse rate in the first 3 days after the regular end of gradual methadone reduction. Thirty-three out of 39 patients achieved a drug-free state: 22 carried a T allele (TT, CT), 11 belonged to the CC genotype group. The pulse rate was significantly (p < 0.05) raised in the T allele group compared to the CC genotype group on the first 2 days after stopping methadone administration. In addition, about a third of the T-allele carriers needed clonidine treatment on the respective days, but only one patient among the 11 CC homozygotes. There was no significant difference between groups in systolic and diastolic blood pressure as well as in subjective withdrawal ratings. A group difference regarding pulse rate could be observed in a small sample and despite a higher degree of concomitant clonidine medication in T allele carriers. The failure to detect group differences in blood pressure and self-rated withdrawal symptoms may be attributed to the more complex regulation of blood pressure and the known weak correlation between objective and subjective withdrawal symptoms.