Further evidence for the role of MET in autism susceptibility

• Published in: Neuroscience research 2010-10, Vol.68 (2), p.137-141
• Main Authors: Thanseem, Ismail, Nakamura, Kazuhiko, Miyachi, Taishi, Toyota, Tomoko, Yamada, Satoru, Tsujii, Masatsugu, Tsuchiya, Kenji J., Anitha, Ayyappan, Iwayama, Yoshimi, Yamada, Kazuo, Hattori, Eiji, Matsuzaki, Hideo, Matsumoto, Kaori, Iwata, Yasuhide, Suzuki, Katsuaki, Suda, Shiro, Kawai, Masayoshi, Sugihara, Gen-ichi, Takebayashi, Kiyokazu, Takei, Noriyoshi, Ichikawa, Hironobu, Sugiyama, Toshiro, Yoshikawa, Takeo, Mori, Norio
• Format: Article
• Language: English
• Subjects: Adolescent; Asian Continental Ancestry Group; Association study; Autism spectrum disorder; Candidate gene; Child; Child Development Disorders, Pervasive - genetics; Female; Gene Frequency; Genetic Predisposition to Disease - genetics; Hepatocyte growth factor receptor; Humans; Linkage Disequilibrium; Male; Neurodevelopment; Polymorphism, Single Nucleotide - genetics; Proto-Oncogene Proteins c-met - genetics; Receptors, Growth Factor - genetics; Single nucleotide polymorphism
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2010.06.014

MET receptor tyrosine kinase (MET)-mediated signaling has been implicated in multiple aspects of neocortical and cerebellar neuronal growth and maturation. A promoter functional SNP (rs1858830) that disrupts the transcription of MET has been reported to be strongly associated with autism spectrum disorders (ASD) in the Caucasian population. Here, we performed a trio association study of MET with ASD in Japanese subjects ( n = 126 trios). Based on the HapMap data on the Japanese population, 15 SNPs were chosen for the association study. One SNP located in intron 1, rs38841, showed a nominal association with autism ( p = 0.044; OR = 1.61) when analyzed using the transmission disequilibrium test. To the best of our knowledge, this is the first replication study of the association of MET with autism, in any non-Caucasian population. Association of rs38841 with autism was further confirmed in 252 Caucasian trios from AGRE ( p = 0.0006). An interesting observation is that all three SNPs of MET (rs1858830, rs38845 and rs38841) shown to be associated with autism in three independent studies including the present one, are located towards the 5′end of the gene at a span of 9.4 kb. Our results provide further evidence for a possible role of MET in the pathogenesis of ASD.