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Gene interaction found to make cocaine use more deadly

A specific interaction between two genes combined with cocaine abuse significantly increased risk for mortality, according to study results recently published in Translational Psychiatry. The interaction between the two genes — known to regulate dopamine in the brain — may lead scientists to better understand how to treat mental disorders such as attention-deficit/hyperactivity disorder, bipolar disorder and schizophrenia.

“This study does not address an issue immediately applicable to clinical care, but it does demonstrate that variations in just a few genes can have dramatic effects on drug response,” study researcher Wolfgang Sadee, PhD, of the department of pharmacology and director of the program in pharmacogenomics at The Ohio State University, told Psychiatric Annals. “Whether the finding with cocaine and risk of death upon abuse can apply to clinical use of drugs targeting the dopamine system, such as antipsychotics and stimulants (amphetamine), remains to be determined, but unusual drug effects can arise from genetic differences.”

 

Wolfgang Sadee

Sadee and colleagues examined brain tissue samples of 126 people who died of cocaine overdose and 99 who died of non-drug related causes. Specifically, the researchers studied variants found in two genes — the dopamine receptor DRD2, which is targeted by psychiatric medication, and the dopamine transporter DAT, which is the primary target of cocaine and amphetamines. Logistic regression analyses were used to determine the association between cocaine-induced death and the combination of the gene variants.

Results indicated that specific mutations in the DRD2 and DAT alleles combined with cocaine abuse conferred a nearly eightfold increased risk for death (OR=7.5; 95% CI, 2.3-25). The increased risk as a result of the gene-gene-environment interaction was mostly found in whites. In fact, some gene variants may have had protective properties for blacks, according to Sadee and colleagues. The researchers estimated that one-in-three whites who died of cocaine overdose were carriers of the variants that make cocaine use so deadly.

According to the researchers, these types of gene-gene interactions could shed light on the heritability of certain disorders and how patients will respond to medication.

“This study exemplifies a promising approach in the search for biomarkers that can serve as guide for optimal therapies of individual patients in psychiatry,” Sadee said.

Disclosure: Sadee reports no relevant financial disclosures.