Genetic association between Notch4 polymorphisms and Japanese schizophrenics.
The objective of this study was to investigate whether three single nucleotide polymorphisms of the Notch4 gene are associated with the onset of schizophrenia. To confirm the linkage disequilibrium among these three single nucleotide polymorphisms of the gene, the three single nucleotide polymorphisms were genotyped by a polymerase chain reaction-restriction-fragment length polymorphism method for all samples. The genotypic frequencies of each single nucleotide polymorphism in the schizophrenic were compared with respective controls using a chi method. To check linkage disequilibrium, the haplotype frequency program was utilized. No statistical association between the two single nucleotide polymorphisms of the Notch4 gene and schizophrenia was observed in our Japanese samples. Although one nonsynonymous single nucleotide polymorphism did show a weakly significant P-value, its allelic frequencies are not positive. Two of the single nucleotide polymorphisms showed strong linkage disequilibrium in our Japanese samples. The single nucleotide polymorphism between the other two single nucleotide polymorphisms showed a weaker linkage disequilibrium with the others. Our study suggests that the three single nucleotide polymorphisms are not associated with the onset of schizophrenia. The linkage disequilibrium of this locus indicates that there is genetic heterogeneity in the Notch4 gene. Linkage disequilibrium may differ among ethnic groups, and so a larger study should be performed in this region.
Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan. nobuto.shibata@nifty.ne.jp
Nobuto
N
Shibata
Tohru
T
Ohnuma
Shinji
S
Higashi
Maiko
M
Higashi
Chie
C
Usui
Taku
T
Ohkubo
Tomoko
T
Watanabe
Akiyoshi
A
Kitajima
Akira
A
Ueki
Masatsugu
M
Nagao
Heii
H
Arai
D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D016009:Chi-Square Distribution; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
D020121:5' Untranslated Regions; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch