Genetic Studies of Inflammatory Bowel Disease

Status:	Completed
Conditions:	Irritable Bowel Syndrome (IBS), Gastrointestinal
Therapuetic Areas:	Gastroenterology
Healthy:	No
Age Range:	Any
Updated:	4/21/2016
Start Date:	November 2003
End Date:	September 2007

Genetic Study of Inflammatory Bowel Disease

This study will examine the existence of genetic regions that are believed to bring about a
risk for inflammatory bowel disease (IBD), with its subtypes of Crohn's disease and
ulcerative colitis. It will identify the locations of chromosomes responsible for hereditary
IBD through linkage analysis, a technique in genetic research in which the occurrence of a
disorder in a family is evaluated alongside a known genetic disorder. The project will also
do fine mapping of genes and examine possible genes associated with IBD.

IBD is a chronic and often disabling disorder of the gastrointestinal tract, affecting about
500,000 Americans. Both Crohn's disease and ulcerative colitis share many characteristics,
such as abdominal pain, bloody diarrhea, fever, fatigue, and malnutrition. But the main
factors that distinguish these subtypes depend on the location and depth of inflammation.
Tests and analyses can generally pinpoint some of the differences between the two, but
sometimes there are major overlaps in characteristics, and the diagnosis is known as
indeterminate IBD. The exact cause of IBD is not known, but genetic and environmental
factors are known to contribute to risk for the disease. The single most important
environmental risk factor has been smoking exposure at the time the diagnosis is made. Also,
several genetic risk factors are ethnicity, family history, and polymorphisms-abilities to
take on different forms-in the NOD2 gene.

Patients who have a diagnosis of IBD and their family members 5 years of age and older who
have or do not have that diagnosis may be eligible for this study.

Participants will be asked to complete a questionnaire on their health, ethnic background,
religion, habits, family medical history, and medications. Information will also be sought
on the diagnosis, course, complications, and treatment of IBD, as well as risk factors. In
addition, there will be collection of blood to be used for DNA preparation, storage of
lymphocytes, and information on immunology.

Using epidemiological, statistical, and molecular genetic techniques, this proposal is
designed to investigate the existence of genetic regions that are believed to confer a risk
for inflammatory bowel disease (IBD), which consists of two subtypes, Crohn's disease (CD)
and ulcerative colitis (UC). The project will derive its study population, consisting of IBD
physician confirmed affected probands with their family members, from the Johns Hopkins
University, the University of Chicago, and the University of Pittsburgh. The project will
consist of multiple parts. The first part is a reanalysis of existing genome wide linkage
data from IBD families with 377 genotyped microsatellite marker data that incorporates
covariate data into the analysis, with the goal of identifying new and refining previously
identified regions of linkage. Eventually this may be extended to include new families typed
for genome wide scan markers. The second part of the project consists of the fine mapping of
the IBD3 locus (HLA region on chromosome 6p), which has been shown to have evidence of
linkage in UC patients. Fifty-two microsatellite markers spanning the affected child trios
in an effort to identify potential marker alleles that may be associated with UC, using the
IBD3 locus will be genotyped in a study population consisting of 240 UC
father-mother-affected child trios in an effort to identify potential marker alleles that
may be associated with UC, using the transmission disequilibrium test, and to identify
potential haplotypes that may confer an increased risk of developing UC, using a
likelihood-based approach where a moving window of adjacent markers will be tested for
excessive transmission. Additional candidate genes within IBD3 will be examined, and
polymorphisms will also be tested for potential significant associations. Eventually this
second part may be extended to fine mapping and association analysis of other candidate
genes and/or candidate regions.

- INCLUSION CRITERIA:

Participants who have a diagnosis of IBD and their family members who have or do not have
a diagnosis of IBD will be recruited for this study. Those further selected to be included
in the linkage study must have at least two affected family members who are willing to
donate blood samples and to fill out medical questionnaires.

EXCLUSION CRITERIA:

Children who were under the age of 5 years were excluded from the Johns Hopkins University
recruitment protocol. There was no age restriction for the University of Chicago or the
University of Pittsburgh. Those who were not able to provide consent were excluded from
the study.

We found this trial at

sites

Johns Hopkins University School of Medicine

733 North Broadway
Baltimore, Maryland 21205

(410) 955-3182