A major international research group — including scientists from Israel’s Hebrew University of Jerusalem and University of Haifa — has discovered a genetic mutation associated with Crohn’s disease, an inflammatory bowel disease (IBD) that affects between three and 14 people out of every 100,000 in any given year.

The study, published in the journal Science Translational Medicine, shows that people who carry the mutation in the LRRK2 gene are at high risk of developing the disease.

Surprisingly, this mutation has already been identified in the past as a factor increasing the risk of developing Parkinson’s disease.

Prof. Gil Atzmon of the University of Haifa, one of the partners in the study, explains: “The practical significance is that we can already identify carriers of the gene at a young age and recognize that they are in a risk group and need constant monitoring and adjustment of lifestyle in the hope to lower the chance of disease outbreak.”

Prof. Gil Atzmon. Photo courtesy of the University of Haifa

Crohn’s is particularly prevalent in two main age groups: 15 to 30 years and 60 to 80 years. The reasons for the development of the disease remain unclear, but may involve a combination of environmental, genetic and immune factors.

“The 1.6 million Americans who suffer from IBD have long been searching for answers when it comes to the painful and confounding conditions that afflict them, including Crohn’s disease,” said Karen Berman, CEO of American Society of the University of Haifa.

The study involving some 50 researchers from Israel, the United States, Canada and the UK sought to examine whether any mutations of specific genes are more common among Crohn’s patients. The initial examination related to 5,700 people of Ashkenazi Jewish origin, including both Crohn’s patients and those without the disease.

Atzmon explains that the genetic affinity among Ashkenazi Jews makes them a kind of “family” in genetic terms, thereby facilitating the identification of a clear association between gene mutations and the expression of the disease.

Moreover, Crohn’s disease is particularly prevalent among Ashkenazi Jews, and they are the ideal group to study the impact of genetic changes.

After the findings were obtained, the researchers examined the genetic association among a much larger group of some 25,000 subjects from around the world.

The findings showed that a specific mutation in the LRRK2 gene creates a statistically significant distinction between those with and without Crohn’s disease. The mutation is almost twice as prevalent among patients as among people without Crohn’s.

Atzmon suggests that since the mutation leads to functional changes in the coded protein, the probability that a carrier of the mutation will develop the disease is particularly high.

Connection between Crohn’s and Parkinson’s

The finding that the same mutation also increases the probability of developing Parkinson’s was unexpected, according to Atzmon, since to date researchers have not identified any similar or associated mechanisms involved in Crohn’s, a bowel disease, and Parkinson’s, a degenerative brain disease.

“One possibility is that there is no connection, and that this gene is responsible for different and unrelated functions in the body. Another possibility we examined is that the enhanced expression of an area in this gene encourages phosphorylation, influencing a cascade of events each of which leads in turn to the outbreak of either or both of these diseases,” said Atzmon.

The significance of the new finding is that it will be possible to use a relatively simple genetic test at a very young age to determine whether someone is a carrier of this genetic mutation. If they are, medical monitoring will enable intervention in the early stages of the development of Crohn’s disease.

Even more importantly, carriers will have the opportunity to adjust their lifestyle habits in order to reduce drastically the chance of an outbreak of Crohn’s – for example, by quitting smoking (or not starting to smoke), trying to reduce stress and emotional anguish, avoiding processed industrial food, and so forth.

“In the longer term,” Atzmon concluded, “the development of a drug that can respond both to the risk of Crohn’s and the risk of Parkinson’s could be a real breakthrough that will be beneficial for large numbers of people.”

The other Israeli researcher in the study was Shai Carmi of the Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem.