Gene Mutations May Increase Adverse Event Risk in Older Adults Taking Multiple Meds

Pharmacogenetic testing may help identify older adults at risk of adverse events, hospitalizations

NEW YORK, NY (Nov. 2, 2016)— Gene mutations that affect drug metabolism may explain higher hospitalization rates for some older adults taking multiple medications, according to researchers from Columbia University.

The study was published recently in Pharmacogenetics and Personalized Medicine.

Use of multiple medications, known as polypharmacy, is on the rise among U.S. seniors. Nearly 40 percent of Americans 65 or older take at least five or more medications. Previous studies have shown that older adults with polypharmacy are more prone to adverse events and hospitalizations than those taking fewer medications. However, few studies have investigated individual, genetic risk factors for adverse drug events in this population.

For this small pilot study, the researchers hypothesized that older adults with polypharmacy and increased hospitalization rates would have more genes associated with altered drug metabolism or lack of sensitivity to certain drugs than those with fewer hospitalizations.

The researchers performed pharmacogenetic testing to identify five such genes—CYP2C19, CYP2C9, VKORC1, CYP2D6, CYP3A4/5—in older adults with polypharmacy. The study included six seniors who had been admitted to the hospital at least three times over the past two years and six age-matched controls who had fewer hospitalizations. Both groups had an average age of 77 years and were taking an average of 14 medications.

In the higher hospitalization group, each of the participants had at least one of the mutations, and half had more than one. None of the controls had any of the mutations.

“Although this was a very small pilot study, the findings suggest that routine testing for these gene variants could improve health outcomes for older adults taking multiple medications,” according to Joseph Finkelstein, MD, PhD, director of the Center for Bioinformatics and Data Analytics in Oral Health at the Columbia University College of Dental Medicine, associate professor of health informatics in dentistry at Columbia University Medical Center, and lead author of the paper. “In dentistry, for example, pharmacogenetic testing could be part of a personalized approach in which clinicians select pain medications that are most effective and least risky for each patient.”

Because of the small size of the pilot study, Dr. Finkelstein and his colleagues are planning a larger clinical trial to investigate whether identification of drug-metabolism-altering mutations in adults with polypharmacy may improve outcomes.



The study is titled, “Pharmacogenetic polymorphism as an independent risk factor for frequent hospitalizations in older adults with polypharmacy: a pilot study.” Authors: Joseph Finkelstein, Carol Friedman, and George Hripcsak (Department of Bioinformatics, Columbia University Medical Center), and Manuel Cabrera (Columbia University College of Physicians & Surgeons).

The authors declare no conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center.  For more information, visit or

Columbia University College of Dental Medicine, among the first university-affiliated dental schools in the United States, was founded in 1916. As part of a world-class medical center, the school trains general dentists and dental specialists in a setting that emphasizes the interconnection between oral health care and overall health for both individuals and communities. The school supports research to advance personalized, evidence-based oral health care and contribute to the professional knowledge base for future oral health leaders. In its commitment to service learning, the school provides dental care to underserved communities of Northern Manhattan and also engages in dental care and local oral health care capacity-building initiatives abroad. Its faculty has played a leadership role in advancing the inclusion of oral health programs in national health-care policy and has developed novel programs to expand oral care locally and in developing countries. For more information, visit