Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review.
Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.
van der Zwaluw
Carmen S
CS
Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands. c.vanderzwaluw@bsi.ru.nl
Engels
Rutger C M E
RC
Buitelaar
Jan
J
Verkes
Robbert J
RJ
Franke
Barbara
B
Scholte
Ron H J
RH
D000430:Alcohol Withdrawal Delirium / Q000235:genetics*; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018076:DNA, Complementary / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004777:Environment; D005190:Family; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D012727:Sex Characteristics; D020080:Tandem Repeat Sequences
D018076:DNA, Complementary; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human