Genetic Trait Could Triple Odds of Whites' Susceptibility to Heavy Cocaine Abuse

Nearly one in five whites could carry a genetic variant that substantially increases their odds of being susceptible to severe cocaine abuse, according to new research.

This genetic variant, characterized by one or both of two tiny gene mutations, alters the brain’s response to specific chemical signals. In the study, led by Ohio State University researchers, the variant was associated with a more than threefold increase in the odds that carriers will be susceptible to severe cocaine abuse leading to fatal overdosing, compared to non-carriers.

Among whites, one or both mutations were found in more than 40 percent of autopsy brain samples taken from people who had abused cocaine, compared to 19 percent of samples from people who lived drug-free.

Overall, one in five samples from whites in the control group and one in two to three samples in the cocaine overdose group contained the genetic variant, compared to one in eight African Americans, in whom the variant is less prevalent.

The mutations – either alone or in combination – affect how dopamine modulates brain activity. Dopamine, a neurotransmitter, is a chemical messenger vital to the regular function of the central nervous system. Previous research has established that cocaine blocks dopamine transporters from absorbing dopamine after its release, leaving the chemical outside the brain cells and creating a feeling of euphoria.

In people who carry one or both of the mutations, the function of a gene responsible for transmitting dopamine signals in the brain is altered. Researchers speculate that this altered gene function sets up a vicious circle of chemical signals that could lead to a craving for a substance that can maintain elevated levels of dopamine in the brain.

The researchers say many questions about cocaine abuse susceptibility remain unanswered: Do the mutations increase the chances someone will try cocaine in the first place? Or do they deepen the cocaine craving and lead to heavy abuse? And how strong is the overall effect of this trait?

But what the research does show is the first strong connection in brain tissue between the mutations and the presence of severe cocaine abuse.

“We now have both good biological rationale and clinical association showing that this has an impact on the way cocaine abuse might progress or might be initiated,” said Wolfgang Sadee, professor of pharmacology and director of the Program in Pharmacogenomics at Ohio State and senior author of the study. “We have found a frequent variant in one of the key candidate genes that can affect cocaine abuse, but more importantly, it also opens the avenue to explore how this variant affects response to therapies for a variety of psychiatric disorders that involve dopamine.”

The research appears online and is scheduled for later print publication in the journal Neuropsychopharmacology.