The zinc finger and DHHC domain-containing protein 8 (ZDHHC8) gene is located on chromosome 22q11, which several genome scans have provided repeated evidence for a significant linkage with bipolar disorder (BPD) and schizophrenia. A recent study revealed that a single nucleotide polymorphism (SNP), rs175174, which has potential effects on splicing, in intron 4 of the ZDHHC8 gene is associated with susceptibility to patients with schizophrenia in US and South Africa. We examined three SNPs of the ZDHHC8 gene, including rs175174, by case-control association in Japanese patients with BPD (N=172) and controls (N=298) or patients with schizophrenia (N=407) and controls (N=497). No significant association with BPD or schizophrenia was observed. After stratification by subcategories, bipolar I and II of BPD, and paranoid and disorganized types of schizophrenia, no significant association was found, nor was a significant association with either disorder found after dividing by gender. These data suggest that the ZDHHC8 gene may not be associated with susceptibility to BPD or schizophrenia, at least in a Japanese population.
"Therefore, in the current study, we investigated the association of ZDHHC8 rs175174 with schizophrenia and cortical volumes. The frequencies of the minor allele-G were 0.4393 and 0.4344 in control and patient groups, respectively, similar to European populations (Faul et al., 2005; Glaser et al., 2005), but lower than Asian populations (Chen et al., 2004; Otani et al., 2005; Saito et al., 2005). Probably, these differences were due to our admixed sample, which presented a higher European ancestry component than African and Native-American/Asian ancestries. "
[Show abstract][Hide abstract] ABSTRACT: ZDHHC8 rs175174 polymorphism is located in 22q11.2 region and its role in brain volume has not been fully addressed. A total of 282 schizophrenia patients and 379 controls were genotyped. A sample of 138 patients underwent brain MRI scan. No association was found between schizophrenia and genotypes. Nevertheless, GG-genotype carriers presented gray matter volume (GMV) reduction in frontal lobe compared to A-allele carriers, and cerebellar hemispheres GMV reductions were found in G-allele carriers compared to AA-genotype. Moreover, A-allele carriers presented posterior brain GMV reductions when compared to GG-genotype. These data suggest that ZDHHC8 may play a role in cortical volumes.
Schizophrenia Research 04/2013; 145(1-3):33-5. DOI:10.1016/j.schres.2013.01.011 · 3.92 Impact Factor
"Although polymorphisms in the ZDHHC8 gene have been reported to be associated with the risk of schizophrenia, those associations are still very controversial. Some results provide evidence that rs175174 would not be a susceptibility factor for schizophrenia in the Japanese population (Otani et al., 2005; Saito et al., 2005) and some other results indicate that there is no association between the SNP rs175174 and schizophrenia in the European Caucasian population (Glaser et al., 2005). The background of the discrepancy among studies in the role of rs175174 of the ZDHHC8 gene in schizophrenia remains to be resolved in future studies . "
[Show abstract][Hide abstract] ABSTRACT: Palmitoylation is one of the most common posttranslational lipid modifications of proteins and we now know quite a lot about it. However, the state of knowledge about the enzymes that catalyze this process is clearly insufficient. This review is focused on 23 human DHHC genes and their products - protein palmitoyltransferases. Here we describe mainly the structure and function of these proteins, but also, to a lesser degree, what the substrates of the enzymes are and whether they are related to various diseases. The main aim of this review was to catalogue existing information concerning the human DHHC family of genes/proteins, making them and their functions easier to understand.
European journal of cell biology 12/2011; 91(2):107-17. DOI:10.1016/j.ejcb.2011.09.013 · 3.83 Impact Factor
"Regarding ZDHHC8, two studies reported significant association between specific gene variants and schizophrenia (Liu et al. 2002; Mukai et al. 2004). These results were not confirmed in further studies in the Japanese and European populations (Glaser et al. 2006b; Otani et al. 2005; Saito et al. 2005). Xu et al. (Xu et al. 2010) performed a meta-analysis and found a negative association between ZDHHC8 polymorphism and schizophrenia. "
[Show abstract][Hide abstract] ABSTRACT: 22q11.2 Deletion syndrome has become an important model for understanding the pathophysiology of neurodevelopmental conditions, particularly schizophrenia which develops in about 20-25% of individuals with a chromosome 22q11.2 microdeletion. From the initial discovery of the syndrome, associated developmental delays made it clear that changes in brain development were a key part of the expression. Once patients were followed through childhood into adult years, further neurobehavioural phenotypes became apparent, including a changing cognitive profile, anxiety disorders and seizure diathesis. The variability of expression is as wide as for the myriad physical features associated with the syndrome, with the addition of evolving phenotype over the developmental trajectory. Notably, variability appears unrelated to length of the associated deletion. Several mouse models of the deletion have been engineered and are beginning to reveal potential molecular mechanisms for the cognitive and behavioural phenotypes observable in animals. Both animal and human studies hold great promise for further discoveries relevant to neurodevelopment and associated cognitive, behavioural and psychiatric disorders.
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