"Hitchhikers" Bring Bowel Disease

Crohn's disease linked to gene OCTN1

(RxWiki News) Human evolution is not always a tidy process. Sometimes, a genetic change makes it easier for our species to survive. At other times, genetic changes can lead to disease and death.

Crohn's disease - a painful bowel disorder - may be linked to a genetic change that happened in humans who grew the first food crops.

There are many factors that put people at risk for Crohn's disease, but it is unknown how many of these risk factors actually cause the disease, says Stephen L. Guthery, M.D., from the University of Utah and Primary Children's Medical Center in Salt Lake City, and senior author of the study.

"Crohn's disease may be linked from your parents and grandparents."

Past studies have found a link between a gene called OCTN1 and Crohn's disease. Guthery and colleagues set out to focus on this gene.

Their research describes a story that happened to the humans who grew the first domesticated crops about 12,000 years ago. At some point, these humans were not getting enough of a certain part of their diet - specifically, an antioxidant called ergothioneine. As a result, a genetic change occurred over time to make up for this loss in their diet. At the same time, other genetic changes were brought along in a process known as "genetic hitchhiking."

In the course of evolution, certain genes are selected to change. Genetic hitchhiking happens when one gene selected for change carries with it a bunch of other genetic changes.

In the case of Crohn's disease, it appears that a change to help humans absorb more ergothioneine carried with it a genetic change that increases the risk of Crohn's disease.

Most people think evolution is how animals and humans better adapt to their environments, says Chad D. Huff, Ph.D., a postdoctoral fellow in human genetics at the University of Utah and lead author of the study. When adaptations happen quickly, however, the genetic changes can be inefficient or even harmful. This kind of change may be what happened about 12,000 years ago and what is today a genetic risk for Crohn's disease, explains Huff.

There are many parts of the human genome to play a role in Crohn's disease. But it is hard to tell which specific gene is the root cause. Dr. Guthery, Huff, and colleagues focused on one part of the genome called IBD5. In IBD5, there are many genetic changes that happen at different rates that are linked to Crohn's disease, which makes it hard to tell which gene is the cause.

While past studies have found links between OCTN1 and Crohn's disease, this study suggests that many genetic changes are carried along when OCTN1 is selected. The study's authors believe that it is not OCTN1 that puts people at risk for Crohn's. Rather, it is changes in IRF1 - a "hitchhiker" gene of OCTN1 - that put people at risk for the disease.

They came to these results by looking at the genes of 1,868 cases of Crohn's disease and 5,550 cases without Crohn's disease. They studied chromosomes with both the OCTN1 mutation and the genetic hitchhikers near IRF1. They also study chromosomes with the OCTN1 mutation but without the genetic hitchhikers.

In the end, the researchers found that OCTN1 was only associated with Crohn's disease if it also was with the IRF1 hitchhikers. This suggests that OCTN1 is not the specific risk factor for Crohn's disease. Instead, the risk is from the IRF1 hitchhikers.

This study is published online in Molecular Biology and Evolution.

Review Date: 
August 9, 2011