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U of U study: 'Hitchhiking' gene plays important role in Crohn's disease

U of U study: 'Hitchhiking' gene plays important role in Crohn's disease


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SALT LAKE CITY — It began with a stomach ache when Charlotte Shragge was in her 20s.

At the time, she thought it was due to the poor diet of a typical college student. But then it got worse.

"I started getting sick and having a lot of digestive issues," she said. "It got to the point that I didn't even go out in public, it was so debilitating. I really didn't feel safe leaving home and not knowing where I could find the next restroom."

Her parents took her to a doctor and she was ultimately diagnosed with Crohn's disease, a debilitating and painful chronic bowel disorder that affects an estimated 700,000 people in the United States.

Scientists believe there is a genetic link to the disease, but finding a cure remains elusive because its cause is thought to be linked to as many as 70 different genes. One Utah doctor believes his research may bring scientists one small step closer to reaching a better understanding of the causes of Crohn's, and hopefully closer to a cure.

Charlotte Shragge is a Salt Lake resident who suffers from Crohn's disease.
Charlotte Shragge is a Salt Lake resident who suffers from Crohn's disease. (Photo: Laura Seitz, Deseret News)

Now 37, Shragge treats her disease with a variety of drugs, monitoring her stress, and staying away from certain foods when she has a flareup. Still, drugs lose their effectiveness over time and she must be re-evaluated for new ones. Flareups can come on suddenly and can last anywhere from a week to as long as four months.

"Having a chronic disease can be a bit of a roller coaster. I've had long periods of feeling great and I've had other periods of feeling just downright ill, and wondering what the next step is," Shragge said. It's not uncommon for body fatigue and joint pain to settle in as well.

"We've looked at Crohn's disease recurrence in families," said Dr. Stephen Guthery, an associate professor of pediatrics at the University of Utah who also treats Crohn's patients at Primary Children's Medical Center. Guthery said the link among family members is evidence of a genetic risk for Crohn's.

Shragge said after being diagnosed she discovered she had several cousins who also had the condition. She said she recently lost a cousin who suffered from chronic ulcerative colitis and succumbed to colon cancer. She said she wanted to share her story in order to spread awareness.

"It's not something that I'm going to hide or be ashamed of," she said.


What they found was that genetic mutations that allowed early humans to better digest domestic crops had a "hitchhiker" gene that contributes to Crohn's

There are genetic risk factors for a variety of diseases, such as heart disease or obesity. Guthery said with Crohn's there are believed to be around 70 identified genetic risk factors, making it an extremely complex condition to understand.

Taking samples of 100 Utah Crohn's patients, as part of over 1,800 patients across the country and in Russia, Guthery and his group traced protein levels to their genetic origins. What they found was a history that went back as far as the first humans to grow domesticated crops. In a study published this month in the British journal Molecular Biology and Evolution, Guthery and a team of other researchers traced the early origins of a key digestive gene. What they found was that genetic mutations that allowed early humans to better digest domestic crops had a "hitchhiker" gene that contributes to Crohn's.

"Our work suggests that one genetic mutation in this region became common in Europeans because it was beneficial, and that neighboring disease-causing genetic changes hitchhiked and became more common," Guthery said.

The story actually goes back further to the Fertile Crescent area, which is now parts of Iraq, Iran and Israel. Early crops, such as lentils, peas, wheat and barley, were low in the amino acid ergothioneine and humans genetically adapted to better digest the food. However, other mutations also took place.


"It really is kind of like playing Russian roulette," she said.

"In this case, we think an adaptation to a transient change in diet around 12,000 years ago resulted in a genetic predisposition of Crohn's disease that is present in about half of all Europeans today," said Chad Huff, the study's lead author and human genetics research fellow at the U.

"We feel that we're getting closer," Guthery said.

Meanwhile, people like Shragge manage their condition with drugs, diet and exercise. Shragge admits that one of her favorite foods is Mexican. When her condition is dormant, she can handle it just fine, but it's always taking a chance.

"It really is kind of like playing Russian roulette," she said.

Email:gfattah@desnews.com

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Geoffrey Fattah

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