Role of genes, the environment and their interactions in the etiology of inflammatory bowel diseases.
Few of the studied genes demonstrate association with inflammatory bowel disease (IBD). Three mutations in the nucleotide-binding oligomerization domain 2 gene have consistently shown to be independent risk factors for Crohn's disease, but none of the alleles exhibited high sensitivity or specificity for IBD. Linkage analysis implicated several loci on various chromosomes, and epistasis has been demonstrated. The etiopathogenesis of IBD remains unknown, and environmental contribution to their pathogenesis is evident from genetic studies that demonstrated incomplete monozygotic twins concordandance rate for both Crohn's and ulcerative colitis. Smoking has shown an opposite effect on disease phenotype, with an adverse effect on disease course for Crohn's disease, but a slight beneficial effect in ulcerative colitis. The contribution of infectious agents to susceptibility to IBD appears to be strong. However, the role of nutrition on the etiology and therapy of IBD is not clear. Inconsistencies in environmental risk factors could be due to gene-environment interactions, making it essential to study the role of genetics and environmental contribution to the etiopathology of IBD. Transgenic or knockout mice, such as interleukin-10(-/-), T-cell receptor alpha(-/-), Galphai(2) (-/-) and N-cadherin(-/-), develop colitis-like inflammation similar to humans. Therefore, animal models must be further studied to explore mechanistic interactions.
Ahmed
Farid E
FE
The Brody School of Medicine at East Carolina University, Department of Radiation Oncology, Leo W Jenkins Cancer Center, Greenville, NC 27858, USA. ahmedf@mail.ecu.edu
D000818:Animals; D004195:Disease Models, Animal; D004777:Environment; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D025202:Molecular Diagnostic Techniques; D010641:Phenotype; D012307:Risk Factors; D012680:Sensitivity and Specificity