Interaction between NOTCH4 and catechol-O-methyltransferase genotypes in schizophrenia patients with poor response to typical neuroleptics.
OBJECTIVE
In this study we attempted to show that the interaction between NOTCH4 and catechol-O-methyltransferase (COMT) polymorphism predicts the response to typical neuroleptics in schizophrenia. Our sample consisted of 94 Finnish patients with DSM-IV schizophrenia and 98 controls.


METHODS
Several studies have connected COMT and NOTCH4 genes to schizophrenia. We have previously shown that COMT polymorphism is significantly associated with treatment response in schizophrenia. NOTCH4 SNP2 polymorphism has been associated with age of onset in schizophrenia, but there is also a trend that this polymorphism may predict response to typical neuroleptics. In the present sample, there is a strong gene-gene interaction between these genes (P = 0.003) and they have additive effect in treatment response.


RESULTS
Patients carrying both NOTCH4 C/C genotype and COMT low/low genotype, had more than ten times higher risk of being a non-responder than responder to treatment with typical neuroleptics [OR = 10.25 (95% CI 2.21-47.53), P < 0.001]. This combination of genotypes is also more common in patients considered non-responders than in controls [OR = 3.00 (95% CI 1.33-6.76), P = 0.007].


CONCLUSIONS
Our results suggest that an interaction between COMT and NOTCH4 genotypes may predict the treatment response to typical neuroleptics in patients with schizophrenia.
Anttila
Sami
S
University of Tampere, Medical School, 33014 University of Tampere, Finland. samia@koti.soon.fi
Illi
Ari
A
Kampman
Olli
O
Mattila
Kari M
KM
Lehtimäki
Terho
T
Leinonen
Esa
E
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
D014150:Antipsychotic Agents; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D002394:Catechol O-Methyltransferase