Role of genetics in prediction of disease course and response to therapy.

The clinical course of Crohn's disease and ulcerative colitis is highly variable between patients, and this has therapeutic implications. A number of clinical features have been identified, which predict a mild or more severe outcome. However, several of these are subjective and/or not persistent over time. With the progress in genetics research in inflammatory bowel disease (IBD), genetic markers are increasingly being proposed to improve stratification of patients. Genetics have the major advantage of being stable over time and not prone to subjective interpretation. Nevertheless, none of the genetic variants associated with particular outcomes have shown sufficient sensitivity or specificity to have been implemented in daily management. Along the same line of thinking, pharmacogenetics or the study of association between variability in drug response and genetic variation has also received more attention as part of the endeavor for personalized medicine. The ultimate goal in this area of medicine is to adapt medication to a patient's specific genetic background and therefore improve on efficacy and safety rates. Although pharmacogenetic studies have been performed for all classes of drugs applied in IBD, few have generated consistent findings or have been replicated. The only genetic test approved for clinical practice is thiopurine S-methyltransferase testing prior to starting treatment with thiopurine analogues. The other reported associations have suffered from lack of confirmation or still need replication efforts. Nevertheless, the importance and necessity of pharmacogenetic studies will increase further as more therapeutic classes are being developed.