Using the transmission disequilibrium test, the present study examined linkage disequilibrium of alcohol and drug (opioid and/or cocaine) dependence with three DRD2 polymorphic systems: (a) TaqI A, (b) TaqI D, and (c) the functional -141CIns/Del promoter systems.
The data showing a strong association of the minor alleles (A1 and B1) of the DRD2 with cocaine dependence suggest that a gene, located on the q22-q23 region of chromosome 11, confers susceptibility to this drug disorder.
We genotyped the Int8 and 3'UTR variable number of tandem repeats of the dopamine transporter gene (DAT1/SLC6A3), the TaqIA (rs1800497) and TaqIB (rs1079597) SNP polymorphisms within the dopamine receptor D2 gene and the 19-bp insertion/deletion and c.444G>A (rs1108580) polymorphisms of the dopamine β-hydroxylase gene (DBH) in a Spanish sample of 169 patients with cocaine addiction and 169 sex-matched controls.
Since dopamine deficiency has been found with cocaine addiction, our objective was to examine whether functional variants in the ankyrin repeat and kinase domain-containing 1 (ANKK1) and/or the dopamine receptor D2 (DRD2) genes interact with response to treatment with disulfiram.
We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P < 0.05) in Caucasian subjects, but not African-American individuals.
Our data do not support a role for the dopamine D2 receptor gene TaqI A and dopamine D3 receptor gene BalI gene polymorphisms in the susceptibility to cocaine dependence in a Brazilian sample.
In this same group, interaction analysis demonstrated that the presence of DRD2-T allele and concomitant absence of DRD4-7R allele were associated with risk for crack cocaine addiction.
Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DbetaH and DAT1 respectively.
One potential mechanism in humans is suggested by findings that ELS interacts with polymorphisms of the GABRA2 gene, encoding α2 subunits of GABAA receptors, to increase the risk for both post-traumatic stress disorder and vulnerability to cocaine addiction.
The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma.
Since the serotonin transporter (5HTT) may be involved in modulating effects of cocaine, we investigated whether allelic variants of the 5HTT gene may confer susceptibility to cocaine dependence among African-American individuals.
Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction.
This study indicates that a patient's OPRK1 genotype could be used to identify a subset of individuals for whom vaccine treatment may be an effective pharmacotherapy for cocaine dependence.
Here, we examined whether the OPRK1rs6989250 C>G affects stress-induced cocaine craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence.
We genotyped the SLC6A45-HTTLPR (rs4795541, rs25531) and TPH2 1125A>T (rs4290270) variants and evaluated their role in moderating disulfiram treatment for cocaine dependence.
The data point to an important but differential role of the amygdala and dorsal raphe nucleus in 5-HTT genotype-dependent vulnerability to cocaine addiction.
Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.