Are single nucleotide polymorphisms underutilized for guiding treatment of inflammatory bowel disease?

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU), significantly impacts quality of life. Despite significant advances in the management of the conditions, responses to treatments vary greatly, and this is due partly to our natural genetic variation. Here we will review the evidence for whether single nucleotide polymorphisms (SNPs) have the potential to guide treatment decisions for people with IBD. We will first consider SNPs that exhibit strong associations with IBD pathogenesis and their relevance to epithelial barrier integrity, cytokine production, and immune system function. Then, we will cover those SNPs implicated in altering response to our various current IBD therapeutics, including the recently implemented drugs ustekinumab and tofacitinib. Finally, we will explore lesser-known SNPs that exhibit complex relationships with the disease and which may be undervalued as pharmacogenetic tools. Overall, it will be demonstrated that SNPs associated with IBD pathology are largely distinct from those predicting response to treatments and that new discoveries of clinically useful tools can be expected from therapy-focused investigations. Given the growing list of treatments available, we argue that beneficial personalization of treatments based on SNPs is still underutilized.