How do Genetic Differences in Immunosuppressive Drug Metabolism Impact Outcomes for Liver Transplant

Principal investigator: Pranab Barman, MD  Variations in our genetic makeup determine who we are, from hair and eye color to how we respond to drugs. Today, the growing field of personalized medicine looks to our DNA to tailor treatment so that we receive precise and appropriate care. An emerging offshoot, pharmacogenomics looks specifically at the connections between genetics and drug metabolism. Liver transplant recipients must take immunosuppressive medications for a lifetime to prevent organ rejection. Due to unique genetic profiles, though, one drug often does not fit all. The differences in how these medicines are absorbed by individual recipient’s intestines and then processed by the liver range from harmful to ineffective. Too high a dosage—potential kidney problems. Too low a dosage—potential rejection of the new organ. Given the shortage of donor livers in this country and the long wait list of recipients, ensuring the success of every liver transplant is critically important. Thanks to a grant from the Digestive Health Foundation, researchers in Northwestern Medicine’s Division of Gastroenterology and Hepatology will evaluate the impact of drug metabolizing genes on patient outcomes after liver transplant. Taking advantage of Northwestern Medicine’s extensive biobank, the investigators will study blood samples previously collected from 50 liver transplant recipients. They hope to better understand the links between genetics and drug metabolism for this specific patient population. Pranab Barman, MD, and his research team are conducting pharmacogenomic studies focusing on seven specific genes associated with drug metabolism. Analyzing genetic variations between patients, the researchers plan to identify how much the recipient intestine and donor liver independently contribute to metabolizing these crucial medications. The ability to...