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Genetic trait could triple odds of whites' susceptibility to heavy cocaine abuse
Date:12/21/2010

the genes' functions long before protein production begins.

In this work, Sadee and colleagues examined allele differences in a gene called dopamine receptor D2. This receptor has a short form and a long form, each of which has a distinct function in the process of regulating dopamine after it is released so its levels stay normal in the brain.

In people who carry these polymorphisms, however, the ratio of the short form to long form of the gene is disrupted. One mutation shortens the short form, and the other lengthens the long form. When this happens with either one or both of the SNPs, most of the short form of the gene is wiped out, and the receptor's dopamine regulatory role malfunctions.

Sadee's lab identified these SNPs and showed in previous studies that their presence influenced cognitive processing, another brain function that is affected by dopamine. The researchers then turned to behaviors and disorders associated with dopamine regulation, including cocaine abuse.

To test the clinical relevance of the SNPs, the researchers examined human brain autopsy tissues of people who had died of cocaine overdose and from age-matched drug-free controls. The researchers used a technique that measures for what is known as allelic messenger RNA expression imbalance, which was developed in Sadee's pharmacogenomics core lab.

Among whites, more than 40 percent of the samples taken from people who had abused cocaine contained these polymorphisms, compared to less than one in five of the drug-free brain samples.

The finding suggests that whites with at least one of these mutations are 3.4 times more likely to be susceptible to cocaine abuse than are whites without either mutation. The study suggested that whites with both mutations, known as homozygous carriers, are at even higher risk for susceptibility to cocaine abuse, but the results were not significant when subjected to statistical analysis, meaning this higher
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Contact: Wolfgang Sadee
wolfgang.sadee@osumc.edu
614-292-1597
Ohio State University
Source:Eurekalert

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