Genetic polymorphisms related to delirium tremens: a systematic review.
BACKGROUND
Delirium tremens (DT) is one of the more severe complications of alcohol withdrawal (AW), with a 5 to 10% lifetime risk for alcohol-dependent patients. The 2 most important neurosystems involved in AW are gamma-aminobutyric acid and glutamate. It is unknown whether these neurosystems are involved in the pathophysiology of DT as well. The candidate gene approach in DT could contribute to this knowledge and demonstrate a possible genetic predisposition for DT. The purpose of this study is to give an overview of all studied genetic polymorphisms in the diverse candidate genes related to DT and to summarize what these studies contribute to insights into the pathophysiology of DT.


METHODS
The inclusion criteria for this literature study were articles in English analyzing the association between a genetic polymorphism and DT without other AW syndromes. Studies were identified until February 2006 in MEDLINE and EMBASE databases.


RESULTS
We found 25 studies dealing with 30 polymorphisms, located in 19 different genes. Positive associations were found in 3 different candidate genes involved in the dopamine transmission, 1 gene involved in the glutamate pathway, 1 neuropeptide gene, and 1 cannabinoid gene. Two candidate genes involved in the dopamine transmission, dopamine receptor D3, and solute carrier family 6, were each associated with DT in 2 different study populations. The other 4 positive associations were not replicated in other studies.


CONCLUSIONS
A total of 8 positive associations out of 30 polymorphisms makes a genetic base for DT plausible. Understanding the pathophysiological process of the development of DT has, indeed, been augmented by the reviewed genetic association studies. These studies suggest that the regulation of dopaminergic neurotransmission may play an important role.
van Munster
Barbara C
BC
Department of Clinical Epidemiology and Biostatistics Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. b.c.vanmunster@amc.uva.nl
Korevaar
Johanna C
JC
de Rooij
Sophia E
SE
Levi
Marcel
M
Zwinderman
Aeilko H
AH
D000430:Alcohol Withdrawal Delirium / Q000235:genetics* / Q000503:physiopathology*; D016022:Case-Control Studies; D019992:Databases as Topic; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
C493593:DRD3 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D050637:Receptors, Dopamine D3; C493214:SLC6A3 protein, human