Study identifies genetic variable affecting African-American methadone patients

Researchers at Yale University have uncovered potentially important information to shed light on the difficult balance in achieving optimal dosing of methadone for opioid dependence. They have identified a genetic variant that appears to be linked to a need for higher doses of the medication in African-Americans.

This finding, from a study published last week in Molecular Psychiatry, carries importance because other research has shown that opioid treatment programs serving a large number of African-Americans tend to report more under-dosing of methadone, the researchers explained. The Yale study did not find the same genetic link among methadone patients of European descent.

“We found specific gene effects in people with African ancestry, an understudied population,” senior author Joel Gelernter, MD, Foundations Fund Professor of Psychiatry at the Yale School of Medicine, said in a university news release.

Details of study

The researchers conducted a genome-wide association study to search for pharmacogenetic determinants of daily methadone dose in a group of opioid treatment patients. Proper dosing of methadone can be painstaking, as opioid treatment programs seek to provide clinical benefit to patients while limiting the risk of sedation or respiratory depression from an excessively high dose.

DNA was extracted from opioid-dependent patients who had received methadone, and each study participant was asked about what their usual dose of the medication had been. For comparison purposes, the researchers also conducted a genomic analysis of children who had received intravenous morphine during surgery.

The researchers found that a genetic variant proximate to the gene OPRM1 was associated with a higher daily methadone dose in the opioid-dependent African-American population. Similarly, this genetic variant also predicted the morphine dose required to achieve effective pain control in the young African-American surgery patients. These associations were not seen in the study's patients of European ancestry.

With the researchers stating that they observed lower doses of both methadone and morphine in African-American patients, they wrote in the journal article that their findings are consistent with the hypothesis that “prescriber bias may contribute to differences between population groups in the quantity of opioids dispensed, although we cannot exclude the possibility that the observed differences in dosing may reflect actual differences in medication requirements.”