The (CTG)n polymorphism in the NOTCH4 gene is not associated with schizophrenia in Japanese individuals.
BACKGROUND
The human NOTCH4 gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiological roles. In a British linkage study, NOTCH4 gene polymorphisms were highly associated with schizophrenia. In a Japanese case-control association study, however, these polymorphisms did not show significant associations with schizophrenia. We conducted a case-control study with Japanese subjects to explore an association between the triplet repeat polymorphism in the NOTCH4 gene and schizophrenia, including subtypes of schizophrenia, longitudinal disease course characteristics, and a positive family history for psychoses.


METHODS
We examined the (CTG)n repeat polymorphism in the NOTCH4 gene among 100 healthy Japanese individuals and 102 patients with schizophrenia (22 paranoid, 38 disorganized, 29 residual, 64 episodic, 31 continuous, 42 with prominent negative symptoms, and 46 with positive family histories) using a polymerase chain reaction-based, single-strand conformational polymorphism analysis.


RESULTS
Five different alleles consisting of 6, 9, 10, 11, and 13 repeats of CTG (Leu) in patients with schizophrenia, and 4 alleles consisting of 6, 9, 10, and 11 repeats in controls were found. No significant differences in genotype or allele frequencies of repeat numbers were found between controls and patients. In addition, there were no associations between the polymorphism and schizophrenia subtypes, longitudinal disease course characteristics, or positive family history of the patients.


CONCLUSIONS
Our data suggest a lack of association between the NOTCH4 gene triplet repeat polymorphism and schizophrenia in Japanese individuals.
Imai
K
K
Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan. zc6k-imi@asahi-net.or.jp
Harada
S
S
Kawanishi
Y
Y
Tachikawa
H
H
Okubo
T
T
Suzuki
T
T
D000328:Adult; D044466:Asian People / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018911:Trinucleotide Repeats / Q000235:genetics
C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch