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Genetic Testing For Ulcerative Colitis

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Inflammatory Bowel Disease Subpanel

Predictive Genetic Testing in Clinical Practice Conners Story


Inflammatory bowel disease is comprised of ulcerative colitis, Crohns disease and unclassified IBD. In the United States, it is currently estimated that 1.3% of adults have been diagnosed with IBD. The main symptoms may include diarrhea, abdominal pain, weight loss, bloody stool, fever, fatigue, and reduced appetite. However, ulcerative colitis is confined to the colon while Crohns disease can be a multi-organ disorder, affecting the entire gastrointestinal tract and sometimes exhibiting involvement from the eyes, liver, joints, and additional body systems. Diagnosis may occur at any stage in life although most symptoms develop before 30 years old. IBD is more prevalent amongst individuals with Ashkenazi Jewish background.

The Inflammatory bowel disease Subpanel includes 59 genes and is offered as a subpanel of the Comprehensive Immunodeficiency Panel . The disorders included in this panel may be inherited in an autosomal dominant , autosomal recessive , or X-linked manner.

The Common Thread By Noel R Rose Md Phd

Chairman Emeritus, AARDA National Scientific Advisory Board Professor of Pathology and of Molecular Microbiology and Immunology Director, Center for Autoimmune Disease Research, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD if you have a genetic predisposition to autoimmunity, you may have twice or five times as much chance of developing autoimmunity as someone elsenot 100 times, but not zero. So genetics plays an important role

Organic Cation Transporter 1/2

OCTN1 and OCTN2 are widely expressed , but specifically expressed in principal intestinal cell types affected by CD: epithelial cells, CD68+ macrophages and CD43+ T cells. SLC22A4 and SLC22A5 encode the polytopic transmembrane sodium-dependent carnitine and sodium-independent organic cation transporters OCTN1 and OCTN2. OCTNs have important role in the maintenance of intracellular homeostasis and in the energy production of the cell . Both OCTNs play important role in the maintenance of gastrointestinal health and in the prevention of gut inflammation.

CD associated variants, the T1672C and -207G were as strongly associated with UC in unrelated Caucasian subjects.

Homozygous patients for the 1672T variant were significantly associated with UC in a study cohort from Italy, suggesting that OCTN1 could have a role in modulating the severity of chronic inflammation in UC.

The mutation that leads to L503F substitution in the OCTN1 protein can alter the transporters activity. Only a weak gender-specific effect of L503F was observed at male UC patients in a cohort of familial and sporadic IBD from the central Pennsylvania, United States.

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Heres What We Do Know:

  • Men and women are equally likely to be affected.

  • The disease can occur at any age, but Crohns disease is most prevalent in adolescents and adults between the ages of 15 and 35.

  • Diet and stress may aggravate Crohns disease, but do not cause the disease.

  • Recent research suggests hereditary, genetic, and environmental factors contribute to Crohns disease development.

Current And Future Role Of Serogenomics In Ulcerative Colitis

DNA and Your Diet: Can Genomic Testing Help Manage UC?

Dr. Flasar is an Assistant Professor of Medicine in the Division of Gastroenterology and Hepatology at the University of Maryland School of Medicine and a staff physician in the Gastroenterology Section of the Veterans Affairs, Maryland Health Care System, both in Baltimore, Maryland. Dr. Cross is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at the University of Maryland School of Medicine and Chief of the Gastroenterology Section of the Veterans Affairs, Maryland Health Care System, both in Baltimore, Maryland.

Dr. Doman is a Clinical Professor of Medicine in the Division of Gastroenterology at George Washington University School of Medicine in Washington, DC.

Address correspondence to:

Dr. Mark H. Flasar, 100 North Greene Street, Lower Level, Baltimore, MD 21201 Tel: 410-706-3387 Fax: 410-706-4330 E-mail:

Genetics of Ulcerative Colitis

Population-based and twin studies have long supported the notion of a genetic contribution to the development of UC.3 Despite early findings confirming that the major histocompatibility complex region on chromosome 6 is important in determining susceptibility for UC and associations with extensive disease, significant progress in clarifying and detailing this association had been relatively limited.4,5 However, recent technologic advances have promoted rapid growth in the study of the genetics of UC.

Serologic Markers in Ulcerative Colitis

Related Biomarkers

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Genetic Testing In Ibd Patients

G& H Can you briefly summarize the reasoning behind the hypothesis of a genetic component to inflammatory bowel disease?

DR Two historic observations have been made that have led to the assumption of a genetic component to inflammatory bowel disease . The first was the observation of families in which multiple members had IBD and that, within these families, the type of inflammatory disease, location in the bowel where it manifests, age at diagnosis, and sometimes even extraintestinal manifestations, were similar. In and of itself, this finding does not confirm a genetic association because if this were an environmental cause , one might anticipate a similar exposure among multiple family members as well.

However, the other historical observation providing a clue to the genetic component of IBD is that Ashkenazi Jewish individuals have a four- to five-fold increased risk of developing IBD than do non-Jewish whites. This suggests what is considered a population-genetics or ethnic-genetics influence in the disease. Subsequently, family studies, linkage analysis, and gene mapping have all confirmed an important genetic component to the disease.

G& H Are genetic factors the only variables in the development of IBD?

G& H Is there a single gene that offers the most compelling evidence for a genetic component?

G& H How is the discovery of the NOD2/CARD15 gene being utilized in ongoing research?

G& H Are other genes being examined or is current research limited to NOD2?

A Note About Sex And Gender

Sex and gender exist on spectrums. This article will use the terms male, female, or both to refer to sex assigned at birth. .

found 242 susceptibility loci DNA sequence for IBD. Experts associated 50 of these with very early onset inflammatory disease. A 2019 study also found six genes responsible for the progression of UC.

UC also shares a genetic architecture with multiple sclerosis, another autoimmune-mediated disease, according to a 2021 study.

There are also other factors linking genetics to an increased susceptibility to having UC, including:

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Signal Transducer And Activator Of Transcription 3

In a large GWAS study the rs12948909 SNPs in the STAT3 locus was identified and found to be strongly associated with UC in the United Kingdom population.

In the Hungarian population the STAT3 rs744166 was investigated. STAT3 rs744166 TT genotype and T allele frequencies were significantly higher in patients with UC than in controls. Logistic regression analysis revealed that the TT genotype confers as an increased risk for the development of UC.

In a North American study the same polymorphisms were tested, but no significant differences were found between the UC group and healthy controls .

Quick Answers For Clinicians

When Can Genetic Testing be Utilized in our IBD Patients? Pediatric IBD Patients?

Differentiating between Crohn disease and ulcerative colitis can be challenging, but features such as rectal bleeding and anemia are more common in UC than CD, whereas perianal involvement, stenosis, abscesses, and fistulas are more common in CD than UC. Distinguishing the two diseases generally requires endoscopic evaluation and/or imaging. Serologic testing may help to differentiate between inflammatory bowel disease subtypes , but this testing is not highly sensitive, which limits its usefulness. Serologic antibody testing is not currently recommended by the American College of Gastroenterology for IBD diagnosis. The ACG also discourages the use of serologic testing to predict disease course or severity in UC. However, serologic response to certain microbial antigens is a recognized risk factor for progression in CD therefore, serologic testing may aid in the risk stratification of patients with CD. See Serologic Markers.

Although some genetic variants are associated with specific inflammatory bowel disease phenotypes, genetic testing has not been found to be of significant benefit for IBD diagnosis or prognosis. Genetic testing is primarily used for therapeutic decision-making in IBD because variants in TPMT and NUDT15 genes can affect how patients metabolize thiopurine drugs used for IBD treatment. See Thiopurine Therapy-Related Testing.

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Ppi Networks And Functional Enrichment Analysis

We accessed gene biological knowledge, protein functional associations, and PPIs with respect to genetic function, using a web-based analytic tool. The analysis flowchart as flowing that: the gene ontology functions enrichment was extracted from the DAVID database2 for annotation, visualization, and integrated discovery bioinformatics resources GO terms for which p< 0.05 were considered to be significantly enriched in the gene modules of interest and the network of Kyoto Encyclopedia of Genes and Genomes pathway was identified form Metascape database3 , and p< 0.05 and enrichment score > 1.0 was set as the cut-off criteria after carried out for the genes enriched in KEGG pathway of immunity, inflammation and tumorigenesis for the interesting gene modules, we subsequently constructed the PPI biological networks based on the STRING online database with the nodes association confidence score > 0.4 . In addition, the Cytoscape software was used to visualize and evaluate interactions and identifying the hub gene in functional networks . The top 10 highest-degree nodes were defined as functional hub genes in the PPI network.

Environmental Risk Factors And Ulcerative Colitis

There is a limited effect of genetics on UC development and an increasing incidence of UC around the world, suggesting that environmental factors are likely more important to disease development and severity than genetic factors. Environmental risk factors may include:

  • Former cigarette smoking
  • Personal history of gastrointestinal, colorectal, or digestive diseases
  • Use of some medications, such as birth control pills, hormone replacement therapy, or nonsteroidal anti-inflammatory drugs

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Current Research On Ulcerative Colitis

Most people that suffer from the condition have relatives with the disease. However, the genetic factors that influence it are complex and need more research to understand completely.

Researchers have had difficulty pinpointing the genes responsible for UC as suspected genes tend to be related to other Inherited Bowel diseases such as Crohns and other types of infection. However, the clustering of IBD, which majorly includes Crohns and ulcerative cancer, has suggested that people who develop both diseases seem to have a relationship with a relative, including distant family members.

Generally, about 10 to 25 percent of people with UC have a parent or sibling with IBD . The risk of UC is also higher among more distant relatives, like grandparents and cousins. UC that affects multiple family members often starts at an earlier age than in people with no family history of the condition.

A study from 2012 titled New Genetic Links for Crohns and Colitis discovered that many genes related to host-microbe interactions have a strong IBD relationship. The group studied both Crohns Disease and Ulcerative Colitis and acquired raw data that proved that the majority of genetic risk factors are associated with both diseases. Ramnik Xavier, an HMS professor of Medicine and team key member, explained that Crohns Disease and UC might not be two distinct diseases but collections of many different ones.

Significant Gene Module Based On The Wgcna

Ulcerative Colitis

In this study, GSE59071 was used as the training dataset and GSE65114, GSE36807, and GSE37283 were used as the validation datasets. WGCNA package version 1.61 in R3.4.1 was applied to select the significant gene module associated with UC in the four datasets. The WGCNA algorithm is implemented according to the steps of defining adjacency function, dividing gene modules, and evaluating module stability. The threshold of gene module partition and screening is that the gene module contains at least 100 genes with a cut height of 0.995. Genes in the important modules were selected as the object for further analysis.

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Analysis Of Genes Involved In Ulcerative Colitis Activity And Tumorigenesis Through Systematic Mining Of Gene Co

  • 1Department of Gastroenterology, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
  • 2Digestive Endoscopy Center, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
  • 3Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
  • 4Department of Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
  • 5Guangdong Institute of Gastroenterology, Guangdong, China
  • 6Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Investigating The Functional Role And Transcription Factor Of Hub Genes

Importantly, the DAVID7 and Metascape database were used to explore the GO terms and KEGG pathway enrichment analysis of candidate targets, respectively. The enrichment cut-off criteria keep the same with the chapter and Section âPPI Networks and Functional Enrichment Analysis.â Subsequently, to identify the transcription factor of the hub genes, the plug in iRegulon for Cytoscape software was applied, with the parameters were set to: minimum identity between orthologous genes = 0.05 maximum FDR for motif similarity = 0.001 and normalized enrichment score ⥠3.0 . Here, the top three regulators with the highest NES value were detected to construct the regulatory network involved in UC-associated carcinogenesis process.

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Crohns Disease And The Immune System

A persons immune system usually attacks and kills foreign invaders like bacteria, viruses, fungi, and other microorganisms. During a normal immune response, cells travel out of the blood to the intestines and produce inflammation. Under normal circumstances, harmless bacteria thats present in the GI tract are protected from an immune system attack.

Screening Of Expression Profile Data

Ulcerative Colitis, Crohn’s Disease, Diverticulitis – Medical-Surgical – Gastrointestinal System

Ulcerative colitis and Human were used as keywords to search all publicly uploaded expression profile data from the National Center for Biotechnology Information Gene Expression Omnibus database . This study contained four datasets: GSE65114 , GSE36807 , GSE37283 , and GSE59071 . The selection standards of datasets were as follows: the dataset was a gene expression profile, the samples are solid samples of intestinal tissue from UC patients, and the samples contained control samples. Microarray raw data from the four datasets were obtained from the Affymetrix platform , which were processed for background correction and quantile normalization using Affy package in R3.4.1 version 1.60.6 .

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Is Ulcerative Colitis Genetic

Ulcerative colitis is a form of inflammatory bowel disease thought to be brought on by immune system dysfunction. The causes of UC are complex, involving both genetic and environmental factors.

Researchers are still learning about what exactly causes UC. Studies of the human genome show that there is a genetic component to the disease, meaning some hereditary risk factors can increase the chance of developing UC. However, there is still a lot to learn about the specific genes involved and how they affect the pathogenesis of UC.

Although there is a genetic component to colitis, environmental risk factors seem to have a much bigger impact on the development of UC.

Genetic Testing For Early Onset Inflammatory Bowel Disease

Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel disease . These patients often develop symptoms during infancy or early childhood, along with endoscopic and histological features of Crohn’s disease, ulcerative colitis, or unclassified forms of IBD. Our inflammatory bowel disease primary immunodeficiency panel identifies variants within genes known to be associated with IBD and immunodeficiency that can help establish a diagnosis and, in some cases, allow for appropriate management and surveillance for disease features based on the gene involved.

Ann Moyer, M.D., Ph.D., gives an overview of the inflammatory bowel disease primary immunodeficiency testing available through Mayo Clinic Laboratories. She discusses when this testing should be ordered, how this testing improves upon previous testing approaches, and what clinical action can be taken due to the results of this testing.

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Investigating The Functional Role And Tf Of Hub Genes

To further understand how the hub genes were correlated with UC-associated carcinogenesis, we applied DAVID and Metascape online database to explore the biological function. The results of GO term enrichment indicated that the GO:0032496â¼response to lipopolysaccharide , GO:0030816â¼regulation of cAMP metabolic process , and GO:0006954â¼inflammatory/immune response were mainly enriched, while pathway of Ecb04668: TNF signaling pathway , Ecb04062: Chemokine signaling pathway , and Ecb04060: Cytokine-cytokine receptor interaction .

Finally, we predicted TFs and found that nuclear factor NF-kappa-B1 , friend leukemia integration 1 TF , and signal transducer and activator of transcription 1 as the master regulators of the hub genes are involved in UC-associated carcinogenesis .

Nebula Genomics Dna Report For Ulcerative Colitis

PredictImmune: a blood test to tailor treatment for bowel condition ...

Is ulcerative colitis genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

This information has been updated to reflect recent scientific research as of October 2021

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Screening Of Degs With Significant Consistency By Meta

First, we perform data standardization on each of the 4 datasets, which was shown in Additional file : Table . A total of 16,337 genes were obtained from the four datasets. MetaQC quality-control inspection was conducted on the four datasets . The PCA principal component plan is shown in Fig. A, indicating that the four datasets are evenly distributed. The sum of PC1 and PC2 was 80.90%, and these indexes met the data quality testing standards that should be included in subsequent analysis. Subsequently, 2009 DEGs with obvious consistency were screened from the four datasets for the next analysis . In Fig. B, DEGs screened from four different datasets were consistent in the degree of difference and direction of maladjustment.

Table 1 The information in GSE65114, GSE36807, GSE37283 and GSE59071 datasets

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