title: Further evidence for the role of MET in autism susceptibility.
abstract: 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.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Taishi
authors.initials: T
authors.lastname: Miyachi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Kaori
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Shiro
authors.initials: S
authors.lastname: Suda
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawai
authors.forename: Gen-Ichi
authors.initials: G
authors.lastname: Sugihara
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Takei
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D000293:Adolescent; D044466:Asian People; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*
chemical_list: D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met