Pharmacogenetics of inflammatory bowel disease

The therapeutic efficacy and toxicity of many commonly employed drugs show interindividual variations that relate to several factors, including genetic variability in drug-metabolizing enzymes, transporters or targets. The study of the genetic determinants influencing interindividual variations in drug response is known as pharmacogenetics. The ability to identify, through preliminary genetic screening, the patients most likely to respond positively to a medication should facilitate the best choice of treatment for each patient; drugs likely to exhibit low efficacy or to give negative side-effects can be avoided. Among the medications used for inflammatory bowel disease, the best studied pharmacogenetically is azathioprine. The hematopoietic toxicity of azathioprine is due to single nucleotide polymorphisms in the thiopurine S-methyltransferase enzyme. Additionally, likely gene targets have been investigated to predict the response to glucocorticoids and infliximab, a monoclonal antibody against tumour necrosis factor that induces remission in approximately 30-40% of patients. However, no genetic predictor of response has been identified in either case.