Association study of H2AFZ with schizophrenia in a Japanese case-control sample.
It is widely accepted that malfunction of the N-methyl-D-aspartate (NMDA)-type glutamate receptor may be involved in the pathophysiology of schizophrenia. Several recent microRNA (miRNA) studies have demonstrated that the expression of the glutamate system-related miR-132 and miR-212 is changed in postmortem schizophrenic brains. Here we attempted to obtain further insight into the relationships among schizophrenia, the NMDA receptor, the molecular cascades controlled by these miRNAs and commonly predicted target genes of the two miRNAs. We focused on the H2AFZ (encoding H2A histone family, member Z) gene, whose expression was shown in our screening study to be modified by a schizophrenomimetic NMDA antagonist, phencyclidine. By performing polymerase chain reaction with fluorescent signal detention using the TaqMan system, we examined four tag single nucleotide polymorphisms (SNPs; SNP01-04) located around and within the H2AFZ gene for their genetic association with schizophrenia. The subjects were a Japanese cohort (2,012 patients with schizophrenia and 2,170 control subjects). We did not detect any significant genetic association of these SNPs with schizophrenia in this cohort. However, we observed a significant association of SNP02 (rs2276939) in the male patients with schizophrenia (allelic P = 0.003, genotypic P = 0.008). A haplotype analysis revealed that haplotypes consisting of SNP02-SNP03 (rs10014424)-SNP04 (rs6854536) also showed a significant association in the male patients with schizophrenia (P = 0.018). These associations remained significant even after correction for multiple testing. The present findings suggest that the H2AFZ gene may be a susceptibility factor in male subjects with schizophrenia, and that modification of the H2AFZ signaling pathway warrants further study in terms of the pathophysiology of schizophrenia.
Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, 113-0034, Japan.
Daisuke
D
Jitoku
Naoki
N
Yamamoto
Yoshimi
Y
Iwayama
Tomoko
T
Toyota
Momo
M
Miyagi
Takeshi
T
Enokida
Yuri
Y
Tasaka
Masakazu
M
Umino
Asami
A
Umino
Akihito
A
Uezato
Yasuhide
Y
Iwata
Katsuaki
K
Suzuki
Mitsuru
M
Kikuchi
Tasuku
T
Hashimoto
Nobuhisa
N
Kanahara
Akeo
A
Kurumaji
Takeo
T
Yoshikawa
Toru
T
Nishikawa
D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006657:Histones / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D012727:Sex Characteristics
D006657:Histones; C077020:histone H2A.F-Z