![[ Visit Client Website ]](images/banner.JPG)
Thursday, May 15, 2008
Champagne Terrace/Bordeaux (Novotel London West)
11:30 AM
Background:
In addition to the core behavioral symptoms of autism spectrum disorder (ASD), a subgroup of patients present with chronic gastrointestinal (GI) dysfunction. We recently reported association of a functional MET gene variant with ASD and significantly decreased expression of MET receptor tyrosine kinase protein in temporal cortex of individuals with ASD. MET is a pleiotropic receptor that functions in both brain development and GI repair.
Objectives:
To determine if association of the ASD-associated MET promoter variant may be enriched in a subset of individuals with co-occurring ASD and GI symptoms.
Methods:
Presence of GI symptoms was determined from medical records available from the Autism Genetics Resource Exchange (AGRE). Genetic association analysis was performed on genotypes at the MET promoter variant rs1858830 using the family based association test (FBAT).
Results:
In a sample of 194 families for which GI symptom diagnosis was available, parent-to-child genetic transmission indicated association of the MET rs1858830 ‘C’ allele with both ASD (P=0.044) and GI symptoms (P=0.001). In 99 families containing at least one child with co-occurring ASD and GI symptoms, the MET ‘C’ allele was associated with both ASD (P=0.002) and GI symptoms (P=0.002). In contrast, there was no association of the MET promoter variant in the 95 families lacking a child with co-occurring ASD and GI symptoms (P=0.918). In addition, GI symptoms were more common in individuals of MET rs1858830 genotype C/C in both strata. Thus, GI symptoms were present in 39% of individuals with genotype C/C and 25% of individuals of genotype G/G (χ2=5.447; P=0.020).
Conclusions:
Replication will be necessary, but these data suggest that disrupted MET signaling may contribute to both behavioral and medical dysfunctions, providing increased sensitivity in stratification of children with ASD into unique subgroups for improved treatment.
Supported by: NIMH MH65299 and the Marino Autism Research Institute (PL).
In addition to the core behavioral symptoms of autism spectrum disorder (ASD), a subgroup of patients present with chronic gastrointestinal (GI) dysfunction. We recently reported association of a functional MET gene variant with ASD and significantly decreased expression of MET receptor tyrosine kinase protein in temporal cortex of individuals with ASD. MET is a pleiotropic receptor that functions in both brain development and GI repair.
Objectives:
To determine if association of the ASD-associated MET promoter variant may be enriched in a subset of individuals with co-occurring ASD and GI symptoms.
Methods:
Presence of GI symptoms was determined from medical records available from the Autism Genetics Resource Exchange (AGRE). Genetic association analysis was performed on genotypes at the MET promoter variant rs1858830 using the family based association test (FBAT).
Results:
In a sample of 194 families for which GI symptom diagnosis was available, parent-to-child genetic transmission indicated association of the MET rs1858830 ‘C’ allele with both ASD (P=0.044) and GI symptoms (P=0.001). In 99 families containing at least one child with co-occurring ASD and GI symptoms, the MET ‘C’ allele was associated with both ASD (P=0.002) and GI symptoms (P=0.002). In contrast, there was no association of the MET promoter variant in the 95 families lacking a child with co-occurring ASD and GI symptoms (P=0.918). In addition, GI symptoms were more common in individuals of MET rs1858830 genotype C/C in both strata. Thus, GI symptoms were present in 39% of individuals with genotype C/C and 25% of individuals of genotype G/G (χ2=5.447; P=0.020).
Conclusions:
Replication will be necessary, but these data suggest that disrupted MET signaling may contribute to both behavioral and medical dysfunctions, providing increased sensitivity in stratification of children with ASD into unique subgroups for improved treatment.
Supported by: NIMH MH65299 and the Marino Autism Research Institute (PL).