New IBD Gene Identified

[Guest guest]

Inflammatory Bowel Disease Gene ID'd

Gene Is Likely One of Several Linked to IBD, Researchers Say

http://www.medicinenet.com/script/main/art.asp?articlekey=77142

By Miranda Hitti

WebMD Medical News

Reviewed By Louise Chang, MD

on Thursday, October 26, 2006

Oct. 26, 2006 -- Scientists have spotted what they suspect is the

first of several genes tied to inflammatory bowel disease (IBD).

The gene is called IL23R. It's noted by Yale University's Judy Cho,

MD, and colleagues in Science's early online edition.

Inflammatory bowel disease includes Crohn's disease and ulcerative

colitis. Its exact cause is unknown.

About a million people in the U.S. have IBD, according to the

National Institute of Diabetes and Digestive and Kidney Diseases.

The gene discovery is " not a gene test " for IBD, and it's " not going

to be an immediate panacea " for people with IBD, Cho tells

WebMD. " But we have a lot better information, and the power of

information, I think, is going to hopefully make a difference. "

For instance, the gene findings may eventually lead to new drugs to

treat IBD.

" It basically says, 'OK, let's put this at the top of the list of

things that we should really work on,' " Cho says.

Inflammation Link

" Inflammatory bowel disease is an uncontrolled chronic inflammation

of the intestines, " Cho tells WebMD. " As you might imagine, the

inflammatory process is very complex.

" Imagine a fire where there's all kinds of things that are

contributing to the fire, " Cho says. " The power of genetics is that

it identifies ... the trigger that started the whole process. "

A certain chemical pathway in the body, called the interleukin-23

pathway, was highlighted in other IBD studies, Cho notes.

" Now the genetics says the same thing, " Cho says.

Gene Study

Cho's team checked the DNA of nearly 1,000 people with Crohn's

disease and almost 1,000 people without either form of IBD. All

participants were whites of European descent.

The scientists looked for DNA differences in the patients and the

people without IBD. Several variations of the IL23R gene -- which

rules the interleukin-23 pathway -- stood out.

In particular, people with an uncommon gene variation were two to

four times less likely to have Crohn's disease, Cho says.

" So instead of thinking about the genetics of disease, maybe you

should be thinking about the genetics of health, " Cho says.

Next Steps

Cho and colleagues are continuing their gene studies.

" Undoubtedly, there are other genes " involved in IBD, Cho says. " We

think that there's going to likely be at least several others. "

It will be important to do IBD gene studies in people of other

ethnic backgrounds, she notes.

As for new treatments, drug companies may be able to make antibodies

that block the interleukin-23 pathway.

That strategy would be " very effective at tamping down inflammation,

but it might be almost too potent, " Cho says. " We have the

inflammatory response to fight off infection. "

A better approach might be to mimic the protective gene variant, Cho

suggests.

" You would tamp down inflammation in a way that you're not more

prone to develop infections, " she says, calling the development of

such drugs " a long-term goal. "

Tailoring Treatment

One day, genetics might help predict IBD's severity in patients and

tailor treatment, Cho notes.

" It's a raging debate in IBD: Are we better off when someone gets

newly diagnosed with going with the big guns that potentially have

more side effects, or are we better off starting with the safest

drug that's maybe not as effective as some of the other ones and

stepping up as patients need, " she says.

" If you take a combination of IBD genes and predict these courses,

that might be a logical way of individualizing therapies, or at

least giving patients more information so that they can make

informed decisions about their medical therapies, " Cho says.

SOURCES: Duerr, R. Science, Oct. 26, 2006; online " Science Express "

edition. National Institute of Diabetes and Digestive and Kidney

Diseases: " Assessing Digestive Diseases Research and Treatment

Opportunities. " Judy Cho, MD, associate professor of medicine and

genetics, director, Inflammatory Bowel Disease Center, Yale

University.

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Science. 2006 Oct 26; [Epub ahead of print]

A Genome-Wide Association Study Identifies IL23R as an Inflammatory

Bowel Disease Gene.

Duerr RH, KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ,

Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T,

Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee A,

Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH

Division of Gastroenterology, Hepatology and Nutrition, Department

of Medicine, School of Medicine, University of Pittsburgh, UPMC-PUH,

Mezzanine Level, C-Wing, 200 Lothrop Street, Pittsburgh, PA 15213,

USA; Department of Human Genetics, Graduate School of Public Health,

University of Pittsburgh, Crabtree A300, 130 Desoto Street,

Pittsburgh, PA 15261, USA.

The inflammatory bowel diseases, Crohn's disease and ulcerative

colitis, are common, chronic disorders that cause abdominal pain,

diarrhea, and gastrointestinal bleeding. To identify genetic factors

that might contribute to these disorders, we performed a genome-wide

association study. We found a highly significant association between

Crohn's disease and the IL23R gene on chromosome 1p31, which encodes

a subunit of the receptor for the pro-inflammatory cytokine

interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A,

p.Arg381Gln) confers strong protection against Crohn's disease, and

additional non-coding IL23R variants are independently associated.

Replication studies confirmed IL23R associations in independent

cohorts of patients with Crohn's disease or ulcerative colitis.

These results and previous studies on the pro-inflammatory role of

IL-23 prioritize this signaling pathway as a therapeutic target in

inflammatory bowel disease. PMID: 17068223

_____________________________

Dave

(father of (21); PSC 07/03; UC 08/03)