Researchers have discovered that a common genetic variant of the MET receptor tyrosine kinase on chromosome 7q31 is associated with a 2.27-fold risk of having autism.
This new finding corroborates other works in autism which “indicate altered organization of both the cerebral cortex and the cerebellum, both of which are disrupted in mice with decreased MET signaling activity,” wrote the investigators, who were led by Daniel B. Campbell, Ph.D., of the department of pharmacology at Vanderbilt University in Nashville, Tenn.
“There is co-occurrence of autism with a number of neurological and cognitive disorders, including epilepsy, atypical sleep patterns, and mental retardation. Together with well known dysfunction of cortical information processing, the role of MET signaling in interneuron development is relevant as a central component of the hypothesized GABAergic pathophysiological changes in autism,” Dr. Campbell and his associates said.
The MET gene, which is known for its role in cancer metastasis, is also involved in the regulation of the immune system and in gastrointestinal repair, the investigators said.
The researchers conducted genetic analysis of 743 families who had at least one child with autism (Proc. Natl. Acad. Sci. U.S.A. 2006 Oct. 19 [doi:10.1073/pnas.0605296103]). They found that people with two copies of the MET gene variant were 2.27 times more likely to have autism as were people in the general population.
The risk of autism among study participants who had only one copy of the genetic variant was also high: a relative risk of 1.67 compared with the general population.
In a statement about the study, the researchers noted that the MET gene variant is common, seen in an estimated 47% of the population. However, in the study, Dr. Campbell and his associates emphasized that having the variant is not a stand-alone marker for a diagnosis of autism.
“We hypothesize that the [variant] can, together with other vulnerability genes and epigenetic and environmental factors, precipitate the onset of autism,” they said.
The study was supported in part by a grant from the National Institute of Mental Health and National Institute of Child Health and Human Development.