Genetics of inflammatory bowel disease

Abstract

: Genetic influence in the susceptibility to inflammatory bowel disease (IBD) is suggested by racial, ethnic, and familial aggregation of disease. Increased concordance for IBD in monozygotic compared with dizygotic twins suggests that genetic rather than environmental factors are primarily responsible for the familial aggregation. A dramatically increased risk for IBD in siblings compared with spouses of affected individuals and many instances of temporal and geographic separation of disease onset in affected relatives also suggest that the familial aggregation of IBD is primarily due to genetic factors. The complex genetics of IBD involves incomplete penetrance and probably involves oligogenic inheritance and genetic heterogeneity. Identification of subclinical markers and markers of genetic heterogeneity in IBD to address the likely problems of incomplete penetrance and genetic heterogeneity would greatly simplify the task of finding IBD susceptibility loci in well-designed genetic marker association and linkage studies. Potential subclinical markers and markers of genetic heterogeneity in IBD are reviewed, as are candidate-gene studies. In addition to candidate-gene studies, future studies should include whole genome screening by using polymorphic genetic markers throughout the genome systematically to map IBD-susceptibility loci. Currently available molecular biologic technology with highly informative polymorphic genetic markers should permit successful identification of IBD-susceptibility genes.

Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept

“…The morphological similarities between AF positive cells and lymphoid cells is of major interest as various forms of immune phenomena are believed to play an important role in the pathogenesis of tissue damage both in Crohn's disease and in ulcerative colitis 1314 Furthermore, the use of immunohistochemistry in combination with in situ hybridisation in IBD may provide important information on the various factors involved in the genetics,15 aetiology, or pathogenesis of these diseases 16-18…”

Genetic Analysis of Susceptibility to Dextran Sulfate Sodium-Induced Colitis in Mice

“…A genetic predisposition is evidenced by increased prevalence in certain populations, increased prevalence among first-degree relatives of patients, and a high concordance rate for disease among monozygotic twins (Yang and Rotter, 1992). The search for inflammatory bowel disease susceptibility genes is complicated by complex genetics that involves incomplete penetrance and probably involves oligogenic inheritance and genetic heterogeneity (Duerr, 1996). Candidate gene-directed screening led to association and linkage of inflammatory bowel disease with human leukocyte antigen class I and II alleles (Duerr, 1996).…”

“…The search for inflammatory bowel disease susceptibility genes is complicated by complex genetics that involves incomplete penetrance and probably involves oligogenic inheritance and genetic heterogeneity (Duerr, 1996). Candidate gene-directed screening led to association and linkage of inflammatory bowel disease with human leukocyte antigen class I and II alleles (Duerr, 1996). Other candidate genes that have been implicated in the pathogenesis of inflammatory bowel disease by association studies include genes encoding interleukin-1 receptor antagonist, the transporter associated with antigen processing, the third component of complement, the T cell receptor, and intercellular adhesion molecule-1 (Duerr, 1996), as well as the natural resistance-associated macrophage protein (NRAMP) gene and the DNA repair gene MLH1 .…”

“…Candidate gene-directed screening led to association and linkage of inflammatory bowel disease with human leukocyte antigen class I and II alleles (Duerr, 1996). Other candidate genes that have been implicated in the pathogenesis of inflammatory bowel disease by association studies include genes encoding interleukin-1 receptor antagonist, the transporter associated with antigen processing, the third component of complement, the T cell receptor, and intercellular adhesion molecule-1 (Duerr, 1996), as well as the natural resistance-associated macrophage protein (NRAMP) gene and the DNA repair gene MLH1 . Genome-wide searches recently indicated a susceptibility locus for Crohn disease on chromosome 16 (Hugot et al, 1996) and susceptibility loci for both Crohn disease and ulcerative colitis on chromosomes 3, 7, and 12 (Satsangi et al, 1996a).…”

Monozygotic twins with Crohn’s disease and ulcerative colitis: a unique case report

“…Genetic influences in inflammatory bowel disease are complicated and are likely to involve genetic heterogeneity, oligogenic inheritance, and incomplete penetrance 14. A putative Crohn’s susceptibility locus on chromosome 16 has recently been identified in two independent panels of families with multiple affected members 15.…”