NOTCH4 gene promoter polymorphism is associated with the age of onset in schizophrenia.
OBJECTIVE
The NOTCH4 gene has a promoter polymor-phism at position -25, which leads to the three genotypes TT, CT and CC. These have been suggested to present a novel independent genetic risk factor for schizophrenia. We conducted a prospective case-control study to explore the impact of NOTCH4 T-25C polymorphism on the factors associated with schizophrenia.


METHODS
NOTCH4 gene promoter T-25C polymorphism was determined by polymerase chain reaction among 94 patients with schizophrenia and 94 healthy age-matched and sex-matched blood donors.


RESULTS
The T allele was highly associated with an earlier age of onset in male patients of schizophrenia (Kaplan-Meier log-rank test P<0.0001). Moreover, the male patients carrying the T allele were born significantly more often in June-November compared with other months of the year [odds ratio=3.92 (95% confidence interval=1.025-15.018), P=0.046]. No association was determined, however, between the NOTCH4 gene polymorphism under study and schizophrenia.


CONCLUSIONS
The NOTCH4 T-25C polymorphism has an important effect on the age of onset in schizophrenia and thus may be related to an early pathogenesis of schizophrenia in young patients. Alternatively, these findings may represent a significant genetic marker for managing subgroups and etiological clues in schizophrenia.
Anttila
Sami
S
University of Tampere, Medical School, Tampereen yliopisto, Finland. samia@koti.tpo.fi
Kampman
Olli
O
Illi
Ari
A
Roivas
Markus
M
Mattila
Kari M
KM
Lassila
Vesa
V
Lehtimäki
Terho
T
Leinonen
Esa
E
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012559:Schizophrenia / Q000097:blood / Q000235:genetics*
C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D004247:DNA