No association between polymorphisms in the prostate apoptosis factor-4 gene and cocaine dependence.
OBJECTIVE
A number of studies have investigated the genes underlying dopamine, serotonin, and glutamine neurotransmitter systems in order to find a genetic basis for the pathology of cocaine dependence. The gene that encodes the prostate apoptosis factor-4 (Par-4) protein is located in the 12q21 region and has been shown to directly interact with the D2 dopamine receptor and through such interaction is thought to directly affect the activity of D2 receptors. The aim of this study is to investigate whether polymorphisms in the human Par-4 gene contribute to the etiology of cocaine dependence.


METHODS
To test this hypothesis, we used a case-control design in which the genotype and allele frequencies for five single nucleotide polymorphisms in the human Par-4 gene were compared between cocaine-dependent individuals (n=172) and controls (n=92) of African descent.


RESULTS
The genotype results failed to detect any associations between polymorphisms in the Par-4 gene and the cocaine-dependent phenotype.


CONCLUSIONS
The results of this study suggest that variations in the human Par-4 gene are unlikely to play a major role in the pathophysiology of cocaine dependence. This study, however, should be repeated in larger cocaine-dependent and control populations to determine that this is indeed the case.
Weller
Andrew E
AE
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. aeweller@sas.upenn.edu
Dahl
John P
JP
Lohoff
Falk W
FW
Kampman
Kyle M
KM
Oslin
David W
DW
Dackis
Charles
C
Ferraro
Thomas N
TN
O'Brien
Charles P
CP
Berrettini
Wade H
WH
D000328:Adult; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic
D051017:Apoptosis Regulatory Proteins; C101296:prostate apoptosis response-4 protein