Novel polymorphisms in the promoter region of the neurotrophin-3 gene and their associations with schizophrenia.
Based on the neurodevelopmental hypothesis in the etiology of schizophrenia, neurotrophic factors may be involved in the pathogenesis of the illness. We searched for polymorphisms in the promoter region of the neurotrophin-3 (NTF3) gene by using denaturing high performance liquid chromatography (DHPLC). Six single nucleotide polymorphisms (SNPs) were found. When these polymorphisms were examined for association with schizophrenia, a weakly significant difference was observed in the genotype distribution of the G/- 3004/A polymorphism between 184 schizophrenics and 185 controls (P < 0.05), although no statistically significant association was detected in a family-based sample of 50 trios (schizophrenics and their parents). With respect to the other polymorphisms, there was no significant association with schizophrenia. The G/- 3004/A polymorphism was in linkage disequilibrium with the CA repeat polymorphism in the first intron of the NTF3 gene. When haplotype-based analysis was performed, an increased frequency of the haplotype containing the G(- 3004) and the "A3" ([CA]23) alleles was observed for the schizophrenics compared to controls. Our results suggest that the G(- 3004)-A3 haplotype has a modest effect of giving susceptibility to schizophrenia.
Hattori
Mineko
M
Department of Psychiatry and Genome Research Center, Teikyo University School of Medicine, Tokyo, Japan.
Kunugi
Hiroshi
H
Akahane
Akihisa
A
Tanaka
Hiroshi
H
Ishida
Sugiko
S
Hirose
Tetsuya
T
Morita
Ryoji
R
Yamakawa
Kazuhiro
K
Nanko
Shinichiro
S
D000328:Adult; D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020933:Neurotrophin 3 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D020933:Neurotrophin 3; D004247:DNA