State-of-the-Art Lecture: Genetics of Crohn's disease: lessons from an impaired barrier

摘要

Unravelling the genetic aetiology of complex diseases has become one of the main new challenges of clinical research. Inflammatory barrier disorders that affect either the mucosal surface or the skin have a number of pathophysiological and clinical characteristics in common. Furthermore, regions of genetic linkage that have been identified in independent studies overlap for several of these diseases. Therefore, it may be assumed that some of the genetic factors involved in one disease aetiology may also play a role in others, and that the traditional, organ-based schemes of clinical classification have become questionable. The validity of this assumption notwithstanding, actual progress in identifying genetic variants underlying the diseases in question is still far from being complete. In this chapter our current molecular understanding of the genetic basis of Crohn's disease (CD) will be used as a guide to illustrate the current state of, and future prospects for, inflammatory barrier disease gene discovery, its implications for our understanding of the disease pathophysiology. This chapter will highlight the relevance of molecular genetics for clinical medicine in general.