Clinical and genetic mechanisms linked to adverse drug reactions

Adverse drug reactions are one of the most common reasons for hospitalisation and have been proposed as the fourth to sixth leading cause of death in hospitalised patients. The current knowledge about possible genetic causes of adverse drug reactions is minimal. The Swedegene project aims to identify genetic factors which can explain why certain patients experience adverse drug reactions.

In collaboration between Uppsala University, the Swedish Medical Products Agency and Karolinska Institute, Swedegene has established a database of clinical data and blood samples from about 4600 cases of various adverse drug reactions. Reactions that cause important health problems are selected, e.g., angioedema and cough from ACE-inhibitors, osteonecrosis from bisphosphonates, and weight gain from neuroleptics and antidepressants. Genome-wide association studies are performed using 5000 population controls from the Swedish Twin Registry as well as treated controls.

In 2021, we have further started investigations of possible genetic and immunological factors that can explain why certain individuals experience adverse reactions to Covid19 vaccines.

Identifying genes in which variation influences susceptibility to adverse drug reactions has the obvious value for genetic testing before starting a drug treatment and might also make it easier to screen molecules likely to cause adverse drug reactions at an early stage of the drug development process. Thus, increased knowledge about genetic causes of adverse drug reactions can minimise the risk with drug treatment in the future. Another possibility is the development of drugs targeted at mechanisms involved in adverse drug reactions, e.g., mechanisms involved in weight gain due to neuroleptics and antidepressants may aid the development of drugs for the treatment of obesity. 

Our research group collaborates with several national and international research groups.

The Swedegene staff consists of:

• Mia Wadelius, professor, vetenskaplig ledare

         Klinisk farmakologi, Akademiska sjukhuset, Uppsala

• Pär Hallberg, docent, projektledare

         Klinisk farmakologi, Akademiska sjukhuset, Uppsala

• Håkan Melhus, professor, överläkare
  Klinisk farmakologi, Akademiska sjukhuset, Uppsala
  
• Erik Eliasson, professor, överläkare
  Klinisk farmakologi, Karolinska universitetssjukhuset, Huddinge
  
• Eva Prado, forskningsassistent
  Klinisk farmakologi, Akademiska sjukhuset, Uppsala
  
• Sara Ask, forskningsassistent
  Klinisk farmakologi, Akademiska sjukhuset, Uppsala
  
• Ulrica Ramqvist, forskningssjuksköterska
  Klinisk farmakologi, Akademiska sjukhuset, Uppsala
  
• Hugo Kohnke, biomedicinsk analytiker
  Klinisk farmakologi, Akademiska sjukhuset, Uppsala
  
• Sofia Attelind, apotekare
  Läkemedelsverket, Uppsala
  
• Anders Sundström, epidemiolog
  Läkemedelsverket, Uppsala