Recent Progress in Inflammatory Bowel Disease Genetics
Judy H. Cho
One approach toward understanding the pathophysiology of Crohn’s disease (CD) and
ulcerative colitis (UC) is through genetic linkage and association studies. These
approaches have provided support for general genomic regions (linkage studies) potentially containing inflammatory bowel disease (IBD) genes, as well as specific genetic variants observed at higher allelic frequencies in IBD patients compared to case-matched controls (association studies). Both approaches have been utilized to characterize multiple likely disease associations in IBD. Of particular importance is the association of NOD2/CARD15 variants with CD.1,2 That NOD2/CARD15 likely functions as an intracellular sensing mechanism for a component of bacterial cell wall peptidoglycan3,4 is fully consistent with existing murine models of IBD, where the role of intraluminal bacteria is critical in disease pathogenesis.5 The underlying engine for these advances has been the large amount of sequence information now available on inter-individual differences in genomic DNA structure. In this chapter, we review the epidemiology of IBD, in particular with respect to the insight these data provide on genetic pathogenesis. Following a brief review of the Human Genome Project, we discuss the present state of understanding of IBD pathogenesis as defined by linkage and association studies. Finally, future challenges of defining IBD pathogenesis through genetic approaches are discussed.