SNP analyses of growth factor genes EGF, TGFbeta-1, and HGF reveal haplotypic association of EGF with autism.
Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-beta (TGFbeta) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGFbeta1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGFbeta1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism.
Toyoda
Takao
T
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Nakamura
Kazuhiko
K
Yamada
Kazuo
K
Thanseem
Ismail
I
Anitha
Ayyappan
A
Suda
Shiro
S
Tsujii
Masatsugu
M
Iwayama
Yoshimi
Y
Hattori
Eiji
E
Toyota
Tomoko
T
Miyachi
Taishi
T
Iwata
Yasuhide
Y
Suzuki
Katsuaki
K
Matsuzaki
Hideo
H
Kawai
Masayoshi
M
Sekine
Yoshimoto
Y
Tsuchiya
Kenji
K
Sugihara
Gen-ichi
G
Ouchi
Yasuomi
Y
Sugiyama
Toshiro
T
Takei
Nori
N
Yoshikawa
Takeo
T
Mori
Norio
N
D001321:Autistic Disorder / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics*; D006239:Haplotypes; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor