Genetics and IBD

The aetiology of the chronic inflammatory bowel diseases, Crohn’s disease and ulcerative colitis remains unknown. However, clinical experience, epidemiological studies and molecular genetics have provided strong evidence that both genetic and environmental factors are important in disease pathogenesis.

A positive family history is the strongest known risk factor in the development if Crohn’s disease. The data from European studies allow concordance rates of 37% in monozygotic twins and the relative risk to a sibling of a patient with Crohn’s disease has been estimated as between 25-35 and between 7-17 for ulcerative colitis. Crohn’s disease and ulcerative colitis are related polygenic diseases sharing some but not all susceptibility genes.

Gene-gene and gene-environmental interactions underlie the complexity of clinical presentations in inflammatory bowel disease. Recently huge investments have been made in an attempt to identify genetic determinants in inflammatory bowel disease. The complementary strategies of genome-wide scanning and candidate gene analysis have been remarkably successful in inflammatory bowel disease compared with all other complex diseases. Four regions of linkage have been widely replicated; IBD1 on chromosome 16 (implicated in Crohn’s Disease only), IBD2 on chromosome 12q13, IBD3 (the major histocompatability complex on chromosome 6p23) and IBD4 on chromosome 14q11-12. Recent data from studies suggests that the IBD1 gene has been identified; the Nod 2 gene, involved in NF- B activation, is implicated by these studies and the polymorphisms associated with Crohn’s disease focus interest on the innate immune response to enteric flora.

The current challenge is to translate this scientific progress into real clinical benefit. It is hoped that prediction of drug effects will result from these studies and that it may be possible to decide the optimal treatment for each patient in the light of his genetic make-up.

Further reading:

Gut 2002; 50 (supp3) iii31-6