TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function.
Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function.
Ohi
K
K
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hashimoto
R
R
Yasuda
Y
Y
Kiribayashi
M
M
Iike
N
N
Yoshida
T
T
Azechi
M
M
Ikezawa
K
K
Takahashi
H
H
Morihara
T
T
Ishii
R
R
Tagami
S
S
Iwase
M
M
Okochi
M
M
Kamino
K
K
Kazui
H
H
Tanaka
T
T
Kudo
T
T
Takeda
M
M
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012091:Repetitive Sequences, Nucleic Acid; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D019265:Spectroscopy, Near-Infrared; D035181:TATA-Box Binding Protein / Q000235:genetics*
D035181:TATA-Box Binding Protein