Mutations in the LRRK2 gene, a major genetic factor contributing to Parkinson’s disease, may likely affect the risk for Crohn’s disease, an inflammatory bowel disease, researchers at Mount Sinai in New York discovered.
The results suggest a potential genetic link between Crohn’s disease and Parkinson’s and common disease mechanisms. The findings should help researchers identify which patients are at risk for Crohn’s and aid in the development of new therapies that target these LRRK2 mutations.
“The presence of shared LRRK2 mutations in patients with Crohn’s disease and Parkinson’s disease provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases,” Inga Peter, the study’s lead author, said in a press release.
The study, “Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease,” was published in the journal Science Translational Medicine.
“Crohn’s disease is a complex disorder with multiple genes and environmental factors involved, which disproportionally affects individuals of Ashkenazi Jewish ancestry,” said Peter, a professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
In an attempt to identify new therapeutic targets for this disease, researchers performed a genome-wide association analysis using data from 2,066 patients with Crohn’s and 3,633 healthy individuals, all from Ashkenazi Jewish descent.
The analysis revealed that members of this population carry two mutations in the LRRK2 gene with opposite effects – one has a protective effect while the other increases the risk for Crohn’s.
Because the LRRK2 gene has long been associated with Parkinson’s disease, researchers went on to assess a possible link between the two diseases. They used a much larger study group of 24,570 people with Crohn’s, Parkinson’s, or with no disease. Each individual group had both Jewish and non-Jewish individuals.
Once again, researchers found that patients with Crohn’s disease had a higher prevalence of the the risk mutation, while those without the disease more commonly had the protective mutation. Interestingly, these mutations had similar effects for Parkinson’s patients, and the effects were seen in both Jewish and non-Jewish patients.
“We now demonstrate that these specific nonsynonymous variants in LRRK2 genetically link [Crohn’s disease] to [Parkinson’s disease],” the team wrote.
Overall, “these results point toward potential shared genetic and epidemiological links between these two diseases and can help identify a sub-group of patients with [Crohn’s disease] who are at a higher risk for developing [Parkinson’s disease],” researchers concluded.
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