Clinical pharmacogenetics and osteoporosis

Genetic and environmental factors play important roles for the development of osteoporosis and other diseases, but also for how individuals respond to drug treatment. Starting with the question why the incidence of osteoporosis is so very high in Sweden, we are investigating genetic - and environmental risk factors for this disease. In our pharmacogentic research programs, we look for genetic differences between individual that can explain variable responses to pharmaceutical drug treatments, with the goal to enable personalized drug dosage.

Each year some 18 000 Swedes suffer from hip fracture, the most serious consequence of osteoporosis. Through epidemiological studies we have shown that a high intake of Vitamin A correlates with an increased risk of osteoporosis. We are now trying to identify additional risk factors, and are studying the molecular mechanisms responsible for the bone toxicity of Vitamin A.

The optimal dose of a drug is a balance between efficacy and side effects, and may vary significantly among individuals due to genetic differences. One such drug is warfarin, used worldwide to prevent blood thrombi, that causes excess bleeding in subgroups of patients. Through pharmacogenetic studies we have identified two genes that affect what is the optimal dose, and thereby facilitated a personalized adjustment of warfarin treatment. In similar studies we work with drugs used to treat e.g. Alzheimer's disease and schizophrenia towards the goal to identify genetic markers which can be employed to optimize the dosage for individual patients.