Inflammatory Bowel Disease: A Review of Previous Genetic Studies and the Liverpool Family Data

2015 ◽  
pp. 1-11 ◽  
Author(s):  
R. B. McConnell ◽  
Joan M. Shaw ◽  
Elizabeth J. Whibley ◽  
T. H. McConnell
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Family Data ◽  
Genetic Studies ◽  
Inflammatory Bowel

scholarly journals Inflammatory bowel disease and Parkinson’s disease: common pathophysiological links

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322429 ◽  
Author(s):  
Ho-Su Lee ◽  
Evy Lobbestael ◽  
Séverine Vermeire ◽  
João Sabino ◽  
Isabelle Cleynen
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Population Based ◽  
Leucine Rich Repeat ◽  
Causal Gene ◽  
Genetic Studies ◽  
Inflammatory Bowel ◽  
Shared Genetic

Inflammatory bowel disease and Parkinson’s disease are chronic progressive disorders that mainly affect different organs: the gut and brain, respectively. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the ‘gut–brain axis’. Moreover, recent population-based studies have shown that inflammatory bowel disease might increase the risk of Parkinson's disease. Although the precise mechanisms underlying gut–brain interactions remain elusive, some of the latest findings have begun to explain the link. Several genetic loci are shared between both disorders with a similar direction of effect on the risk of both diseases. The most interesting example is LRRK2 (leucine-rich repeat kinase 2), initially identified as a causal gene in Parkinson's disease, and recently also implicated in Crohn’s disease. In this review, we highlight recent findings on the link between these seemingly unrelated diseases with shared genetic susceptibility. We discuss supporting and conflicting data obtained from epidemiological and genetic studies along with remaining questions and concerns. In addition, we discuss possible biological links including the gut–brain axis, microbiota, autoimmunity, mitochondrial function and autophagy.

scholarly journals Roles of Autophagy-Related Genes in the Pathogenesis of Inflammatory Bowel Disease

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 77 ◽  
Author(s):  
Sup Kim ◽  
Hyuk Eun ◽  
Eun-Kyeong Jo
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Paneth Cell ◽  
Conditional Knockout ◽  
Intestinal Homeostasis ◽  
Genetic Studies ◽  
Inflammatory Bowel ◽  
Direct Targeting ◽  
Catabolic Process

Autophagy is an intracellular catabolic process that is essential for a variety of cellular responses. Due to its role in the maintenance of biological homeostasis in conditions of stress, dysregulation or disruption of autophagy may be linked to human diseases such as inflammatory bowel disease (IBD). IBD is a complicated inflammatory colitis disorder; Crohn’s disease and ulcerative colitis are the principal types. Genetic studies have shown the clinical relevance of several autophagy-related genes (ATGs) in the pathogenesis of IBD. Additionally, recent studies using conditional knockout mice have led to a comprehensive understanding of ATGs that affect intestinal inflammation, Paneth cell abnormality and enteric pathogenic infection during colitis. In this review, we discuss the various ATGs involved in macroautophagy and selective autophagy, including ATG16L1, IRGM, LRRK2, ATG7, p62, optineurin and TFEB in the maintenance of intestinal homeostasis. Although advances have been made regarding the involvement of ATGs in maintaining intestinal homeostasis, determining the precise contribution of autophagy has remained elusive. Recent efforts based on direct targeting of ATGs and autophagy will further facilitate the development of new therapeutic opportunities for IBD.

Reactive arthritis and enteropathic arthropathy

2013 ◽  
pp. 901-910
Author(s):  
J. S. Hill Gaston
Keyword(s):  
Inflammatory Bowel Disease ◽  
Back Pain ◽  
Bowel Disease ◽  
Reactive Arthritis ◽  
Inflammatory Back Pain ◽  
Hla B27 ◽  
Genetic Studies ◽  
Inflammatory Bowel ◽  
Disease Modifying ◽  
Crystal Induced Arthritis

Reactive arthritis (ReA), and enteropathic arthritis secondary to inflammatory bowel disease, are forms of spondyloarthritis, all of which share an association with HLA B27 and can involve both axial and peripheral joints. Genetic studies strongly implicate the cytokines IL-17 and IL-23 in their pathogenesis, and evidence for autoimmunity is lacking. ReA is triggered by particular bacteria, mainly affecting the gut and genitourinary tract, though infections are sometimes asymptomatic. Classically an acute oligo- or monoarthritis with enthesitis occurs, often with inflammatory back pain, though mild polyarthritis can also occur. Septic and crystal-induced arthritis are the principal differential diagnoses. Extra-articular features may aid diagnosis, which otherwise requires laboratory evidence of preceding infection. Bacterial components traffic to the joint (which is nevertheless sterile), and elicit local pro-inflammatory immune responses. Most ReA is self-limiting, but persistent cases may require disease-modifying anti-rheumatic drugs or even biologics.

Bacteria in the pathogenesis of inflammatory bowel disease

2011 ◽  
Vol 39 (4) ◽  
pp. 1067-1072 ◽  
Author(s):  
Paul Flanagan ◽  
Barry J. Campbell ◽  
Jonathan M. Rhodes
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Twin Studies ◽  
Mucosal Barrier ◽  
Pathogenic Role ◽  
Genetic Studies ◽  
Bacterial Interactions ◽  
Risk Alleles ◽  
Inflammatory Bowel

Twin studies have demonstrated the importance of environmental factors in the pathogenesis of inflammatory bowel disease, but progress has been relatively slow in identifying these, with the exception of smoking, which is positively associated with Crohn's disease and negatively associated with ulcerative colitis. Genetic studies have identified risk alleles which are involved in host–bacterial interactions and the mucosal barrier, and evidence is building for a likely pathogenic role for changes in the gut microbiome, with respect to both faecal and mucosa-associated microbiota. Some of these changes may be secondary to inflammation, nevertheless promising new therapeutic targets are beginning to emerge.

scholarly journals Pediatric Inflammatory Bowel Disease

2021 ◽  
Vol 3 (1) ◽  
pp. 11-17
Author(s):  
Rotondo-Trivette S ◽  
Michail S
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Pediatric Patients ◽  
Adult Onset ◽  
Future Directions ◽  
Genetic Studies ◽  
Diagnosis And Management ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel ◽  
Pediatric Onset

Inflammatory bowel disease is an important pediatric disease, with as many as 25% of cases presenting during childhood. In this article, we review the types, etiology epidemiology, presentation, diagnosis, and management of pediatric inflammatory bowel disease. We also highlight the unique aspects of pediatric-onset inflammatory bowel disease versus adult-onset and future directions in this field, such as the use of genetic studies and ultrasound for the management of pediatric patients with inflammatory bowel disease.

Reactive arthritis and enteropathic arthropathy

2013 ◽  
pp. 901-910
Author(s):  
J. S. Hill Gaston
Keyword(s):  
Inflammatory Bowel Disease ◽  
Back Pain ◽  
Bowel Disease ◽  
Reactive Arthritis ◽  
Inflammatory Back Pain ◽  
Hla B27 ◽  
Genetic Studies ◽  
Inflammatory Bowel ◽  
Disease Modifying ◽  
Crystal Induced Arthritis

Reactive arthritis (ReA), and enteropathic arthritis secondary to inflammatory bowel disease, are forms of spondyloarthritis, all of which share an association with HLA B27 and can involve both axial and peripheral joints. Genetic studies strongly implicate the cytokines IL-17 and IL-23 in their pathogenesis, and evidence for autoimmunity is lacking. ReA is triggered by particular bacteria, mainly affecting the gut and genitourinary tract, though infections are sometimes asymptomatic. Classically an acute oligo- or monoarthritis with enthesitis occurs, often with inflammatory back pain, though mild polyarthritis can also occur. Septic and crystal-induced arthritis are the principal differential diagnoses. Extra-articular features may aid diagnosis, which otherwise requires laboratory evidence of preceding infection. Bacterial components traffic to the joint (which is nevertheless sterile), and elicit local pro-inflammatory immune responses. Most ReA is self-limiting, but persistent cases may require disease-modifying anti-rheumatic drugs or even biologics.

scholarly journals Genetic Studies of Inflammatory Bowel Disease-Focusing on Asian Patients

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 404 ◽  
Author(s):  
Sung Chul Park ◽  
Yoon Tae Jeen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Genetic Variants ◽  
Intestinal Inflammation ◽  
Human Leukocyte ◽  
Risk Modeling ◽  
Genetic Studies ◽  
Asian Patients ◽  
Inflammatory Bowel ◽  
Interleukin 23

The pathogenesis of inflammatory bowel disease (IBD) is not well-understood; however, increased and persistent intestinal inflammation, due to inappropriate immune responses that are caused by interactions between genetic factors, gut microbiota, and environmental factors, are thought to lead to IBD. Various studies have identified more than 240 genetic variants related to IBD. These genetic variants are involved in innate and adaptive immunity, autophagy, defective bacterial handing, interleukin-23 and 10 signaling, and so on. According to several epidemiological and clinical studies, the phenotypes and clinical course of IBD differ between Asians and Europeans. Although the risk loci for IBD typically overlap between Asians and Westerners, genetic heterogeneity has been detected in many loci/genes, such as NOD2/CARD15, TNFSF15 and human leukocyte antigen, contributing to the risk of IBD. Thus, although common pathways exist between Westerners and Asians in the development of IBD, their significance may differ for individual pathways. Although genetic studies are not universally applicable in the clinical field, they may be useful for diagnosing and categorizing IBD, predicting therapeutic responses and toxicity to drugs, and assessing prognosis by risk modeling, thereby enabling precision medicine for individual patients.

scholarly journals Subclinical Markers of Human Inflammatory Bowel Disease

1995 ◽  
Vol 9 (3) ◽  
pp. 161-167 ◽  
Author(s):  
Huiying Yang ◽  
Jerome I Rotter
Keyword(s):  
Inflammatory Bowel Disease ◽  
Genetic Marker ◽  
Intestinal Permeability ◽  
Bowel Disease ◽  
Genetic Studies ◽  
Genetic Determination ◽  
Inflammatory Bowel ◽  
Marker Studies ◽  
Genetically Determined ◽  
Subclinical Marker

Genetic studies can be greatly aided by the use of subclinical markers that are closer to the basic defect and thus likely to detect more individuals with the abnormal genotype. At least two approaches are generally used to characterize subclinical markers. One is the family study approach. The detection of subclinical abnormalities in unaffected relatives similar to those found in the probands can distinguish between an inherited predisposition and a secondary abnormality due to the disease process. The second approach is the combination of subclinical marker with genetic marker studies. Specific association of a subclinical marker with a genetic marker indicates genetic determination of the subclinical marker. The identification of a genetically determined subclinical marker can help to define a more homogeneous disease group for genetic studies. The most studied subclinical markers in inflammatory bowel disease (IBD) are antineutrophil cytoplasmic antibodies (ANCAs) for ulcerative colitis (UC) and intestinal permeability for Crohn's disease (CD). Even so, for these as well as several other promising subclinical markers, there is an obvious need for more twin, family and genetic marker studies. An elevated intestinal permeability in a proportion of unaffected relatives of CD patients has been observed in the majority of family studies. ANCAs, a highly specific marker for UC, have been found with a significantly increased prevalence in unaffected relatives of UC patients compared with spouses of the patients. Moreover, the distribution of the ANCAs is familial rather than random, suggesting heterogeneity within UC. In combination with genetic marker studies (human leukocyte antigen [HLA] class II genes), the authors observed a differential association: ANCA-positive UC was associated with DR2, while ANCA-negative UC associated with DR4. These data lead to the conclusion that the heterogeneity indicated by ANCA is genetically determined and that this genetic heterogeneity should be taken into consideration in future genetic, clinical and pathophysiological studies. In the aggregate, these data indicate that the subclinical marker approach is a powerful means for demonstrating genetic and etiological heterogeneity, and can be an important tool to define the etiology and natural history of the various diseases that make up IBD.

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