Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Association study of H2AFZ with schizophrenia in a Japanese case-control sample. 2625 9

Recently, the H2AFZ gene was reported in relation to schizophrenia in Japanese males. A two-stage case-control study was designed to investigate the association of the H2AFZ gene with schizophrenia and its relationship with cognitive function in Han Chinese patients with schizophrenia. This study included a testing set with 1115 patients and 2289 controls and a validation set with 1843 patients and 3155 controls. A total of 10 single-nucleotide polymorphisms (SNPs) in the H2AFZ gene were genotyped, and both independent data sets were analyzed in association with SNP and gender. The rs2276939 SNP was found to be significantly associated with schizophrenia, particularly in males. A similar pattern was observed in our two-stage study on conducting further imputation and haplotype association analyses. In addition, two of the SNPs (rs61203457 and rs2276939) and cognitive functioning were found to interact significantly when processing the perseverative error in the Wisconsin Card Sorting Test. Our findings suggest that the H2AFZ gene may confer a risk for schizophrenia and contribute to the impairment of executive function in Han Chinese patients with schizophrenia. These findings augment our current state of knowledge regarding the risk of schizophrenia and the impairment of cognitive performance in patients with this disorder.
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PMID:Association of common variants in H2AFZ gene with schizophrenia and cognitive function in patients with schizophrenia. 2624 56