The Expanding Universe of Inflammatory Bowel Disease Genetics
The Expanding Universe of Inflammatory Bowel Disease Genetics
Purpose of review: Genetic factors play an important role in the pathogenesis of inflammatory bowel disease. In this review, we will provide an update on the rapid advances in the discovery of inflammatory bowel disease, primarily Crohn's disease, associated genes.
Recent findings: Seven recently published Crohn's disease genome-wide association studies have confirmed prior findings related to the nucleotide-binding oligomerization domain 2 (NOD2) gene and the IBD5 locus. In addition, 10 novel loci have been identified and well replicated.
Summary: Several promising associations between Crohn's disease and gene variants have been identified and replicated, the two most widely replicated being variants in the IL23R and ATG16L1 genes. These findings highlight and further support the importance of the immune system and its interactions with the intestinal microflora in the pathogenesis of inflammatory bowel disease.
The two main forms of inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, are believed to result from the interplay of several factors including genetics, environment, intestinal microflora, and alterations in innate and adaptive immunity. Early epidemiologic evidence for the role of genetic factors in the pathogenesis of IBD came from studies demonstrating higher rates of IBD among individuals of Caucasian and Jewish ethnicity, familial aggregation of IBD, and higher concordance rates of both twins developing IBD in monozygotic compared with dizygotic twins. The search for specific IBD susceptibility genes, however, has been difficult due to complex genetics, including factors such as lack of simple mendelian inheritance patterns, involvement of several genes, and the influence of environmental factors and intestinal microflora on disease development. In addition, there appears to be disease heterogeneity, suggesting that Crohn's disease and ulcerative colitis are not unique single diseases but rather consist of several different subtypes of disease that share similar clinical features.
Abstract and Introduction
Abstract
Purpose of review: Genetic factors play an important role in the pathogenesis of inflammatory bowel disease. In this review, we will provide an update on the rapid advances in the discovery of inflammatory bowel disease, primarily Crohn's disease, associated genes.
Recent findings: Seven recently published Crohn's disease genome-wide association studies have confirmed prior findings related to the nucleotide-binding oligomerization domain 2 (NOD2) gene and the IBD5 locus. In addition, 10 novel loci have been identified and well replicated.
Summary: Several promising associations between Crohn's disease and gene variants have been identified and replicated, the two most widely replicated being variants in the IL23R and ATG16L1 genes. These findings highlight and further support the importance of the immune system and its interactions with the intestinal microflora in the pathogenesis of inflammatory bowel disease.
Introduction
The two main forms of inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, are believed to result from the interplay of several factors including genetics, environment, intestinal microflora, and alterations in innate and adaptive immunity. Early epidemiologic evidence for the role of genetic factors in the pathogenesis of IBD came from studies demonstrating higher rates of IBD among individuals of Caucasian and Jewish ethnicity, familial aggregation of IBD, and higher concordance rates of both twins developing IBD in monozygotic compared with dizygotic twins. The search for specific IBD susceptibility genes, however, has been difficult due to complex genetics, including factors such as lack of simple mendelian inheritance patterns, involvement of several genes, and the influence of environmental factors and intestinal microflora on disease development. In addition, there appears to be disease heterogeneity, suggesting that Crohn's disease and ulcerative colitis are not unique single diseases but rather consist of several different subtypes of disease that share similar clinical features.
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