Association of common variants in H2AFZ gene with schizophrenia and cognitive function in patients with schizophrenia

Abstract

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.

Brain-specific deletion of histone variant H2A.z results in cortical neurogenesis defects and neurodevelopmental disorder

“…We find that H2A.z regulates the recruitment of Setd2 to promote the H3K36me3 levels of the Nkx2–4 promoter, thereby increasing the expression of Nkx2–4, which ultimately controls neuron production and the expansion of the cerebral cortex. Furthermore, the behavioral abnormalities in H2A.z-null mice provide a possible explanation for the deficits found in patients with schizophrenia ( 27 ). In summary, our findings reveal the role of H2A.z in embryonic neurogenesis and dendrite morphogenesis, and how H2A.z loss may lead to various developmental defects and brain disorders ( Supplementary Figure S14 ).…”

“…Some of these contradictions might be explained by local histone modification patterns ( 25 ). In addition, a genome-wide linkage study indicated that the H2A.z gene may be a susceptibility factor for schizophrenia ( 27 ). Schizophrenia comprises a range of neurodevelopmental disorders characterized by mental disorder, delusions and cognitive deficits, with highly heritability ( 28 ).…”

<p>Vital and Distinct Roles of H2A.Z Isoforms in Hepatocellular Carcinoma</p>

“…31 Another research reveals that H2AFZ is significantly related to schizophrenia and plays crucial roles in some biological processes, such as maintenance of heterochromatin euchromatin status and chromosome segregation. 32 In brief, these studies indicate that the two isoforms of H2A.Z are nonredundant and have isoform-specific functions.…”

Puerarin suppresses cell growth and migration in HPV‑positive cervical cancer cells by inhibiting the PI3K/mTOR signaling pathway

“…The function of Bcl-2 regulates programmed cell death (18). Members of the Bcl-2 family are inhibitors of apoptosis (19). Initiator and executor caspases are key molecules associated with regulation of the apoptosis signaling cascade (19).…”

“…Members of the Bcl-2 family are inhibitors of apoptosis (19). Initiator and executor caspases are key molecules associated with regulation of the apoptosis signaling cascade (19). Apoptosis may occur through either the intrinsic or extrinsic signaling pathway (18).…”