New genetic markers for ulcerative colitis identified

January 4, 2009,

An international team led by University of Pittsburgh School of Medicine researchers has identified genetic markers associated with risk for ulcerative colitis. The findings, which appear today as an advance online publication of the journal Nature Genetics, bring researchers closer to understanding the biological pathways involved in the disease and may lead to the development of new treatments that specifically target them.

Ulcerative colitis is a chronic, relapsing disorder that causes inflammation and ulceration in the inner lining of the rectum and large intestine. The most common symptoms are diarrhea (oftentimes bloody) and abdominal pain. Ulcerative colitis and Crohn's disease, another chronic gastrointestinal inflammatory disorder, are the two major forms of inflammatory bowel disease (IBD).

"Ulcerative colitis and Crohn's disease are chronic conditions that impact the day-to-day lives of patients," said senior author of the study Richard H. Duerr, M.D., associate professor of medicine and human genetics at the University of Pittsburgh School of Medicine and Graduate School of Public Health. "IBD is most often diagnosed in the teenage years or early adulthood. While patients usually don't die from IBD, affected individuals live with its debilitating symptoms during the most productive years of their lives."

Because IBD tends to run in families, researchers have long thought that genetic factors play a role. Technology developed in recent years has enabled systematic, genome-wide searches for gene markers associated with common human diseases, and the discovery of more than 30 genetic risk factors for Crohn's disease has been one of the major success stories in this new era of research. While some genetic factors associated with Crohn's disease also predispose individuals to ulcerative colitis, markers specific for ulcerative colitis had yet to be found.

To do so, researchers performed a genome-wide association study of hundreds of thousands of genetic markers using DNA samples from 1,052 individuals with ulcerative colitis and pre-exisiting data from 2,571 controls, all of European ancestry and residing in North America. Several genetic markers on chromosomes 1p36 and 12q15 showed highly significant associations with ulcerative colitis, and the association evidence was replicated in independent European ancestry samples from North America and southern Italy.

Nearby genes implicated as possibly playing a role in ulcerative colitis include the ring finger protein 186 (RNF186), OTU domain containing 3 (OTUD3), and phospholipase A2, group IIE (PLA2G2E) - genes on chromosome 1p36, and the interferon, gamma (IFNG), interleukin 26 (IL26), and interleukin 22 (IL22) genes on chromosome 12q15. RNF186 and OTUD3 are members of gene families involved in protein turnover and diverse cellular processes. PLA2G2E, IFNG, IL26 and IL22 are known to play a role in inflammation and the immune response. The study also found highly suggestive associations between ulcerative colitis and genetic markers on chromosome 7q31 within or near the laminin, beta 1 (LAMB1) gene, which is a member of a gene family known to play a role in intestinal health and disease, and confirmed previously identified associations between ulcerative colitis and genetic variants in the interleukin 23 receptor (IL23R) gene on chromosome 1p31 and the major histocompatibility complex on chromosome 6p21.

"My laboratory is focused on studying the genetic basis for IBD," said Dr. Duerr. "Through genetic mapping, we and our collaborators are successfully identifying regions of the genome that contain IBD genes. The next steps are to understand the functional significance of IBD-associated genetic variants, and then to develop new treatments that specifically target biological pathways implicated by the genetic discoveries. The overall goal of this work is to improve the lives of the millions of patients worldwide that suffer from IBD."

Source: University of Pittsburgh Schools of the Health Sciences

Explore further: Genetic similarity suggests Crohn's disease and ulcerative colitis form a continuum of subtypes in the bowel

Related Stories

Genetic similarity suggests Crohn's disease and ulcerative colitis form a continuum of subtypes in the bowel

October 19, 2015
A new understanding of inflammatory bowel diseases has been prompted by the analysis of genetic and clinical data from more than 30,000 patients. This study reveals that genetic factors affect the location of the inflammation ...

Study advances understanding of colon cancer and colitis

May 17, 2016
Inflammatory bowel disease (IBD), of which Crohn's disease and ulcerative colitis are the main types, is on the increase in the United States, affecting more than 1.6 million people and explaining perhaps the increase in ...

Takayasu arteritis, ulcerative colitis co-occurrence rate high

August 31, 2015
(HealthDay)—Takayasu arteritis (TAK) has a high rate of co-occurrence and genetic overlap with ulcerative colitis (UC), according to a study published in the August issue of Arthritis & Rheumatology.

Scientists identify molecular markers of kidney transplant rejection

March 15, 2016
Despite advances in organ transplant medicine in recent decades, about half of all kidney transplant patients still lose their organ to rejection within 10 years.

Genetically engineered bacteria could help in Crohn's and colitis

November 2, 2012
(Medical Xpress)—A new study in mice has shown that genetically engineered bacteria can protect against inflammatory bowel disease (IBD), which includes a host of conditions including ulcerative colitis and Crohn's disease.

Study on inflammatory bowel disease in First Nations people adds to understanding of disease

April 10, 2012
Inflammatory bowel disease is relatively rare in Canadian First Nations people but common in white people, possibly due to different genetic variants, according to a new study in CMAJ (Canadian Medical Association Journal) ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.