NOTCH4 gene polymorphism and susceptibility to schizophrenia and schizoaffective disorder

The NOTCH4 gene is located at 6p21.3, a site which several studies have sho wn to have significant linkage with schizophrenia. Recently, an exceptional ly strong association was reported between NOTCH4 gene polymorphisms and sc hizophrenia in British patients. We re-examined their findings using a Japa nese population. We genotyped three kinds of polymorphisms, SNP1 in the 5' flanking region, SNP2 in the promoter region and CTG repeats in exon 1 of t he NOTCH4 gene of schizophrenics (N = 188), patients with schizoaffective d isorder (N = 39) and controls (N = 143). Genotypic distributions and alleli c frequencies of SNP1, SNP2 and CTG repeats of the NOTCH4 gene did not show significant associations with schizophrenia or schizoaffective disorder. N either they showed association with schizophrenia subcategories, hebephreni c and paranoid type schizophrenia, nor with subgroups of schizophrenia with and without positive family history of psychoses. The present study found that the NOTCH4 gene does not confer susceptibility to schizophrenia and sc hizoaffective disorders, at least in Japanese subjects, in contrast to the findings in British subjects. (C) 2001 Published by Elsevier Science Irelan d Ltd.