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MET Gene Linked To Autism, GI Problems In Children

March 2, 2009

A single gene variant may be responsible for both autism and gastrointestinal (GI) disorders in some children, according to a new Vanderbilt University Medical Center study.

The study "Distinct Genetic Risk Based on Association of MET in Families With Co-occurring Autism and Gastrointestinal Conditions," published in the journal Pediatrics, suggests that disrupted MET signaling may contribute to the co-occurring medical conditions in some families.

It is well known that GI conditions are common among individuals with autism, but not known if co-occurring GI conditions represent a unique autism subgroup.

Some speculate that GI dysfunction impacts brain development, or that altered nervous system development affects GI function. The MET protein participates in both brain development and GI repair, suggesting that disruption of MET signaling may contribute to both medical conditions.

"For too long, people have been debating the validity of GI problems in children with autism,” said co-author and Vanderbilt Kennedy Center Director Pat Levitt, Ph.D., the Annette Schaffer Eskind Chair and professor of Pharmacology.

“GI disorders don't cause autism. Autism is a disorder of brain development. However, our study brings together genetic risk for autism and co-occurring GI disorders in a way that provides a biologically plausible explanation for why they are seen so often together."

Lead author Daniel Campbell, Ph.D., said the research is providing mounting evidence that the broad term “autism” will soon be divided into separate, more specific categories.

“Among individuals with autism, 30 percent to70 percent also have GI problems including chronic constipation and chronic diarrhea,” Campbell said.

“And, because many of these patients have difficulties with communication, they may ‘act out’ rather than be able to communicate that their ‘tummy hurts.’”

A total of 918 individuals from 214 Autism Genetics Resource Exchange families were studied, each with a complete medical history including GI condition report.

The MET rs1858830 C allele was associated with both autism and GI conditions in 118 families containing at least one child with co-occurring autism and GI conditions. In contrast, there was no association of the MET polymorphism with autism in the 96 families lacking a child with co-occurring autism and GI conditions.

Researchers concluded that a functional genetic variant in the MET gene is more strongly associated with autism specifically in those families where an individual had co-occurring autism and a GI condition.
 

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