Minor genetic differences between individuals change the effect of a common medication, study shows
Medicine has moved a little bit closer to the era of tailor-made treatments, based on the unique genetic profiles of individual patients, according to recent research conducted by Dr Rima Rozen of the Research Institute of the McGill University Health Centre (RI MUHC) at the Montreal Children's Hospital and McGill University. Her study, published June 18 in the journal Pharmacogenetics and Genomics, shows how minor genetic differences between individuals alter the way a common drug affects the body.
Rozen has measured the impact of Methotrexate -- a drug that inhibits the metabolism of folate -- on mice with an altered MTHFR gene, which is a gene crucial for folate metabolism. The results were striking: after treatment with Methotrexate, mice with the altered gene had approximately 20 per cent less hemoglobin and red blood cells than their counterparts with non-altered genes. The altered mice also showed increased susceptibility to liver and kidney damage following treatment.
"We know that these results are applicable to humans because a parallel mutation in the human MTHFR gene affects human folate metabolism similarly. The results demonstrate that medication affects subjects differently according to individual genetic traits," Dr. Rozen explained. "And tests exist to detect this mutation." Genetic testing would allow physicians the modify treatment based on each patient's personal genetic makeup, limiting potential side effects.
In earlier studies, Rozen's laboratory cloned the MTHFR gene and identified the common variant which interferes in folate metabolism in human populations. Between 10 and 15 per cent of the total caucasian population have two copies of the variant in MTHFR. Folate, a form of water-soluble Vitamin B2, is essential to the production of red blood cells and provides protection against spina bifida, other birth defects, and heart disease. Patients with cancer or auto-immune diseases are often treated with medications that affect folate metabolism, but physicians are not trained to verify how patients naturally metabolize folate, even though this could be an important factor in effective treatment.
"This is a first step towards personalized medicine that is based not only on symptoms but also on the patient's own genetic 'baggage,'" Rozen said. "This trend definitely represents the medicine of the future."
Dr. Rima Rozen is a Scientist in the Medical Genetics and Genomics Axis of the RI MUHC at the Montreal Children's Hospital. At McGill University, she holds the positions of Associate Vice-Principal (Research and International Relations) and Professor in the Human Genetics, Pediatrics and Biology Departments.
This study was funded by the Canadian Institutes of Health Research (CIHR) and the U.S. National Institutes of Health (NIH). Students working on Dr. Rozen's study also received scholarships, such as a Turkish Higher Education Council-Hacettepe University Hospital scholarship, a Cole Foundation Award, and a Studentship Award from the Montreal Children's Hospital Research Institute.
The Montreal Children's Hospital (MCH) is the pediatric teaching hospital of the McGill University Health Centre (MUHC) and is affiliated with McGill University. The MCH is a leader in providing a broad spectrum of highly specialized care to newborns, children, and adolescents from across Quebec. Our areas of medical expertise include programs in brain development/behaviour, cardiovascular sciences, critical care, medical genetics and oncology, tertiary medical and surgical services, and trauma care. Fully bilingual, the hospital also promotes multiculturalism and serves an increasingly diverse community in more than 50 languages. The Montreal Children's Hospital sets itself apart with its team approach to innovative patient care. Our health professionals and staff are dedicated to ensuring children and their families receive exceptional health care in a friendly and supportive environment.
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.
The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec. For further details visit: www.muhc.ca/research