Possible link found between Crohn’s and Parkinson’s among Ashkenazi Jews

This discovery could potentially help doctors develop new treatments for Crohn's which will target a particular Ashkenazi gene

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January 14, 2018 09:50
2 minute read.
Mount Sinai hospital

Mount Sinai hospital campus in Manhattan.. (photo credit: Courtesy)

 
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A possible link between Crohn’s and Parkinson’s diseases has been identified in Ashkenazi Jews.

Researchers at Mount Sinai Hospital in Manhattan have found that Jews of European origin who suffer from Crohn’s, a chronic gastroenterological disease, are more likely to carry the LRRK2 gene mutation, which is a leading genetic cause of Parkinson’s, an incurable neurological movement disorder.

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The findings of the team, headed by genetics and genomic sciences researcher Prof. Inga Peter at Mount Sinai’s Icahn School of Medicine, were just published in the journal Science Translational Medicine and featured on the cover. The discovery, they said, could help doctors better understand Crohn’s disease, determine specifically who’s at risk and develop new drugs for treatment and/or prevention by targeting this specific gene.

“Crohn’s is a complex disorder with multiple genes and environmental factors involved, which disproportionality affects individuals of Ashkenazi Jewish ancestry,” Peter explained. “The presence of shared LRRK2 mutations in patients with Crohn’s and Parkinson’s provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.”

They used international data from the last decade up to the present to analyze the occurrence of 230,000 coding genetic mutations in the genome of 2,066 patients with Crohn’s and compared them to 3,633 people without the disorder. All of the study’s subjects were of Ashkenazi descent. They identified mutations in the LRRK2 gene that are more frequently found in Crohn’s disease cases as compared to unaffected individuals.

When they discovered a link between Crohn’s and the LRRK2 gene mutations, they went further to assess the possible genetic link between Crohn’s and Parkinson’s. The team then looked at a much larger sample of 24,570 people including patients with Crohn’s, Parkinson’s and no disease at all (each group consisted of Jewish and non-Jewish subjects).

The study found two mutations of the LRRK2 gene in Crohn’s-disease patients. One, called the “risk mutation,” was more common in patients with Crohn’s, while the other, the “protective mutation,” was more prevalent in patients without the disease. Most Crohn’s sufferers who carried the risk mutation developed the disease on average of six years earlier than those who did not carry this mutation.



The research also shows that more Crohn’s patients with the risk mutation developed the disease in the small intestine, compared to those without the mutation. If the disease starts in the small intestine, it becomes more difficult to manage and often leads to complications and surgeries. The effect of these mutations was observed in both Ashkenazi Jewish populations and non-Jewish populations.

“Defining the biology of naturally occurring protective mutations is quite important, because they define desired outcomes for potentially new therapies,” explained the study’s co-author Dr. Judy Cho, director of the Center for Integrative Studies in Crohn’s disease and the Institute for Personalized Medicine at the Icahn School.

“Identifying genetic mutations associated with disease risk is an effective way to better understand disease mechanisms, identify individuals at risk and develop novel drug targets to treat the disease,” Peter added. “Our research may also help identify individuals who would benefit the most from LRRK2-directed therapies, thereby contributing to the field of personalized medicine.”

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