Gene Variants Could Undermine Treatment of Minorities

UNC researchers have discovered genetic differences between Hispanics and Caucasians that influence how they respond to popular medications. The results, which were gathered in individuals of Central American, Puerto Rican or Mexican descent, suggest that those populations may not gain the most benefit from treatment regimens based on data from mostly white populations.

“These populations are not just identical to whites, and so they shouldn’t be treated identically,” said Howard McLeod, Pharm.D., co-director of the Novel Methodology Core within the NC Translational and Clinical Sciences (NC TraCS) Institute. NC TraCS is UNC’s home to the NIH Clinical and Translational Science Awards (CTSA), a national consortium focused on translating discoveries to medical practice.

“We found a number of variants where there is either a heightened risk or a lowered risk in Hispanics, and we plan to use this information to formulate recommendations for what medications should be administered to what ethnicities.”

The work was made possible by an NIH supplement totaling $892,342, which McLeod shares with Mary Roederer, PharmD, a research assistant professor in the UNC Eshelman School of Pharmacy.

Over the past year, McLeod and Roederer studied the genetic code of 1,000 Hispanic individuals, looking at nearly 2,000 gene variants that are known to have a large impact on risk of toxicity or altered efficacy from commonly used medications.

They found a number of gene variants that confer heightened risk to all Hispanics, such as lowered white blood cell count from the immunosuppressant azathioprine. In contrast, the researchers found that bleeding risk associated with treatment with the antiplatelet drug clopidogrel differed between each of the four Hispanic groups studied (one Central American, one Puerto Rican and two Mexican).

They are now working to validate their findings in larger groups of Hispanic individuals.

“What we want to do is essentially go out and learn what the data look like on the ground, and then do some intervention work,” said McLeod, who is also a Fred N. Eshelman Distinguished Professor of Pharmacy and director of the UNC Institute for Pharmacogenomics and Individualized Therapy.

“We have talked with the Puerto Rican health authorities about expanding this project to do just that. This approach becomes particularly useful when you have to decide between two drugs that seem equally efficacious and cost-effective. Genetic information can tell us when to take a drug that may have been a first-line therapy and make it second-line.”

McLeod and his colleagues are already incorporating their data into medical decision algorithms to generate therapeutic recommendations. So far, they have completed the development and peer review of algorithms for the 10 most common causes of morbidity and mortality in the various Hispanic groups and are in the process of writing the computer code for the conversion of genetic information into medical policy.