Can switching genes on or off lead to Inflammatory Bowel Disease?

What is this research looking at? 

It is thought that environmental factors such as diet and smoking may play a part in causing Inflammatory Bowel Disease by having an effect on genes. Genes are a short sequence of DNA, and contain a particular set of instructions on how to make a particular protein, or carry out a particular function. 

The researchers have already carried out some research looking at marks on genes which can switch them on or off (this is called methylation). They looked for methylation marks on the DNA in blood taken from people with and without Crohn’s. They found that there was a difference in the amount of this mark present on some genes when the two groups of people were compared. 

One of these genes is called RPS6KA2, and it controls various important processes inside cells. People with Crohn’s have less methylation on this gene than people without the condition, and also, more of the product controlled by this gene is found in the intestines of people with Crohn’s. This has led the researchers to propose that people may be more likely to develop Crohn’s when the RPS6KA2 gene loses the methylation marks, which leads to more of the protein being produced. They wish to do a few more experiments to confirm and extend these findings. They want to see whether there is any difference in where the protein controlled by RPS6KA2 is produced in the intestine, and how much is produced. 

We already know that RPS6KA2 helps control a process known as autophagy. Autophagy is important for getting rid of unwanted cell parts, it is like a recycling system, and it is known that it sometimes goes wrong in the cells of patients with Crohn’s. The researchers will use cells grown in the lab to see if changing the amount of the RPS6KA2 protein causes a change in autophagy. If it does then it is an indication that the increased amounts of RPS6KA2 may be triggering people to develop Crohn’s. 

If this research confirms that that RPS6KA2 is involved in Crohn’s, it will allow scientists to focus on this gene in an effort to better understand the disease. It may mean that the gene can be used to help diagnose people with IBD, and may ultimately identify new targets in an effort to better control IBD. 

Conclusions: The researchers found less methylation marks on the RPS6KA2 gene of people with Crohn’s Disease compared to those without the condition. Importantly, they were able to use these marks to distinguish those with Crohn’s from those with other conditions including Irritable Bowel Syndrome (IBS). 

The researchers didn’t find a difference in where the protein is produced and how much is produced in people with Crohn’s compared to those without the condition. The researchers also grew cells in the laboratory and changed the amount of RPS6KA2 in those cells to see if it had an effect on autophagy - their experiments showed that it didn't. 

What do the researchers think this could mean for people with IBD? 

The researchers hope that this study will help us understand what causes IBD. If they can identify a gene which plays a role in IBD, it may be possible to use it to help diagnose IBD patients, and may even lead to the design of new IBD treatments. 

Who is leading the research: Dr ElaineNimmo, IGMM, University of Edinburgh 

Our Funding: £9,926 
Duration: 2 months 
Official title of the application: Investigating the role of RPS6KA2 in Inflammatory Bowel Disease
Tags: Genetics