A genetic region associated with a life-threatening reaction to thiopurine drugs, used to treat various disorders including autoimmune diseases, is reported in a paper published online this week in Nature Genetics. The results may help clinicians identify patients at risk for this adverse drug reaction.
Thiopurines are a class of immunosuppressive drugs often prescribed to patients with inflammatory bowel disorder (IBD). Approximately 4% of patients who are prescribed these drugs develop pancreatitis, a potentially fatal adverse effect approximately 24 days after starting the medication.
Graham Heap and colleagues searched for genetic associations between thiopurine-induced pancreatitis and genetic variants in 172 IBD patients. They found that variants in a region of the genome involved in the acquired immune response were associated with risk of the drug reaction. The region contained variants at two genetic loci, HLA-DQA1 and HLA-DRB1, which are responsible for making proteins that bind antigens to immune cells. This process leads to the production of antibodies. Patients with two copies of each variant had a 17% risk of adverse drug reaction, while patients with one copy each had a 9% risk.