Inflammatory bowel disease: progress toward a gene

Can J Gastroenterol. 2000 Mar;14(3):207-18. doi: 10.1155/2000/361309.

Abstract

The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) is still unknown, but the importance of genetic susceptibility has been clearly shown by epidemiological data from family and twin studies. Linkage studies have identified two susceptibility loci for inflammatory bowel disease (IBD) on chromosomes 12 and 16. Importantly, these linkages have been replicated by independent investigators, and studies of positional candidates within these regions continue, together with fine mapping strategies. Regions of 'suggestive' linkage on chromosomes 1, 3, 4, 6, 7, 10, 22 and X have also been reported in individual studies. Other important candidate genes investigated include the interleukin-1 receptor antagonist, MUC3 and genes of the human leukocyte antigen (HLA) system. The apparently conflicting data in different studies from around the world may be explained by ethnic differences, case mix and genetic heterogeneity. Replicated class II HLA associations include HLA DRB1*0103 and DR2 (DRB1*1502), involved in UC susceptibility, and HLA DRB1*03 and DR4 as resistance alleles for CD and UC respectively. Animal studies have provided insights from targeted mutations and quantitative trait locus analysis. The goals of continuing research include narrowing the regions of linkages and analysis of candidate genes, and possibly the application of newly developed methods using single nucleotide polymorphisms. Advances in IBD genetics hold the potential to provide knowledge about the disease pathogenesis at the molecular level, with ensuing benefits for clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 16
  • Cluster Analysis
  • Colitis, Ulcerative / genetics*
  • Crohn Disease / genetics*
  • Ethnicity / genetics
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Polymorphism, Genetic
  • Twin Studies as Topic

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class II