| 1 | Biol. Psychiatry 2003 Dec 54: 1298-301 |
|---|---|
| PMID | 14643098 |
| Title | Association study of the human FZD3 locus with schizophrenia. |
| Abstract | The FZD3 protein is a transmembrane receptor for secreted Wnt glycoproteins involved in the Wnt signal transduction cascades. The alteration of Wnt signal transduction cascades has been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Because the human FZD3 gene is mapped to chromosome 8p21, which is a potential region containing a gene for schizophrenia, it may play a role in conferring susceptibility to the disease. This study was conducted with the detection of three single nucleotide polymorphisms (SNPs) located within the FZD3 locus by using the polymerase chain reaction-based restriction fragment length polymorphism (RFLP) analysis among 246 schizophrenic family trios of Chinese Han descent.The transmission disequilibrium test (TDT) demonstrated that the three SNPs all showed a preferential transmission with a p value ranging from.0003-.000007. The global chi-squared test for haplotype transmission also showed a strong association (chi(2) = 48.84, df = 7, p <.000001).The strong association between the FZD3 locus and schizophrenia suggests that the gene itself may play a role in underlying schizophrenia, although a nearby gene responsible for predisposing to the illness cannot be ruled out. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Biol. Psychiatry 2003 Dec 54: 1298-301 |
| PMID | 14643098 |
| Title | Association study of the human FZD3 locus with schizophrenia. |
| Abstract | The FZD3 protein is a transmembrane receptor for secreted Wnt glycoproteins involved in the Wnt signal transduction cascades. The alteration of Wnt signal transduction cascades has been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Because the human FZD3 gene is mapped to chromosome 8p21, which is a potential region containing a gene for schizophrenia, it may play a role in conferring susceptibility to the disease. This study was conducted with the detection of three single nucleotide polymorphisms (SNPs) located within the FZD3 locus by using the polymerase chain reaction-based restriction fragment length polymorphism (RFLP) analysis among 246 schizophrenic family trios of Chinese Han descent.The transmission disequilibrium test (TDT) demonstrated that the three SNPs all showed a preferential transmission with a p value ranging from.0003-.000007. The global chi-squared test for haplotype transmission also showed a strong association (chi(2) = 48.84, df = 7, p <.000001).The strong association between the FZD3 locus and schizophrenia suggests that the gene itself may play a role in underlying schizophrenia, although a nearby gene responsible for predisposing to the illness cannot be ruled out. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Neurosci. Lett. 2003 Dec 353: 53-6 |
| PMID | 14642436 |
| Title | The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia. |
| Abstract | Neurodevelopmental abnormalities have been reported in studies on the pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a variety of processes in neurodevelopment, and the frizzled proteins have been identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3 (FZD3) is required for formation of the neural crest and for development of major fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3 gene in patients with schizophrenia and control subjects in the Japanese population. We found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest that dysregulation of the Wnt-signaling pathway may be involved in the susceptibility to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Biol. Psychiatry 2004 Sep 56: 462-5 |
| PMID | 15364045 |
| Title | Genetic and expression analyses of FZD3 in schizophrenia. |
| Abstract | Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples. Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined. Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains. Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Biol. Psychiatry 2004 Sep 56: 462-5 |
| PMID | 15364045 |
| Title | Genetic and expression analyses of FZD3 in schizophrenia. |
| Abstract | Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples. Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined. Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains. Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Neurosci. Lett. 2004 Aug 366: 336-8 |
| PMID | 15288446 |
| Title | Lack of a genetic association between the frizzled-3 gene and schizophrenia in a British population. |
| Abstract | In recent studies, the frizzled-3 (FZD3) locus was found to be associated with schizophrenia in both Japanese and Chinese populations. To validate the initial finding, we detected three single nucleotide polymorphisms (SNPs) present in a 10-kb segment of DNA at the FZD3 locus, as described in a previous study with a Chinese population. We totally recruited 120 British family trios consisting of fathers, mothers and affected offspring with schizophrenia. The transmission disequilibrium test (TDT) did not show allelic association between these three SNPs and schizophrenia. The 3-SNP haplotype system was composed of only 3 individual haplotypes among the 120 family trios and these 3 SNPs were mainly carried by two distinct haplotypes, suggesting that these 3 SNPs may result from a single founding event in history. No association was shown between the 3-SNP haplotypes and schizophrenia. The present results imply that the FZD3 gene is less evolutionary in the British population than in the Chinese population. This may be a possible reason for the failure to replicate the FZD3 finding with the British sample. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004 Aug 129B: 16-9 |
| PMID | 15274031 |
| Title | Positive association of the human frizzled 3 (FZD3) gene haplotype with schizophrenia in Chinese Han population. |
| Abstract | Frizzled 3 (FZD3) gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. The FZD3 is a transmembrane receptor required for Wnt signal transduction cascades that have been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Previous work has showed a strong association between FZD3 locus and schizophrenia in family-based study. To confirm this issue further, we investigated a genetic association between four single nucleotide polymorphisms (SNPs) located in the FZD3 gene and schizophrenia by case-control study using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) in the Chinese Han population. Our studies showed the SNPs rs2323019 and rs880481 have significant differences in both genotype and allele frequencies between control subjects and schizophrenic patients (rs2323019: Allele A > G, chi2 = 6.7277, df = 1, P = 0.0095; Genotype, chi2 = 10.6583, df = 2, P = 0.0049; rs880481: Allele A > G, chi2 = 10.3945, df = 1, P = 0.0013; Genotype, chi2 = 16.8049, df = 2, P = 0.0002). In addition, we constructed three-locus haplotypes to test their association with schizophrenia. The globe chi-squared test for haplotype analysis showed a significant association (chi2 = 66.38, df = 7, P < 0.000001). These results suggested that the FZD3 gene might be involved in the predisposition to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2004 Aug 129B: 16-9 |
| PMID | 15274031 |
| Title | Positive association of the human frizzled 3 (FZD3) gene haplotype with schizophrenia in Chinese Han population. |
| Abstract | Frizzled 3 (FZD3) gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. The FZD3 is a transmembrane receptor required for Wnt signal transduction cascades that have been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Previous work has showed a strong association between FZD3 locus and schizophrenia in family-based study. To confirm this issue further, we investigated a genetic association between four single nucleotide polymorphisms (SNPs) located in the FZD3 gene and schizophrenia by case-control study using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) in the Chinese Han population. Our studies showed the SNPs rs2323019 and rs880481 have significant differences in both genotype and allele frequencies between control subjects and schizophrenic patients (rs2323019: Allele A > G, chi2 = 6.7277, df = 1, P = 0.0095; Genotype, chi2 = 10.6583, df = 2, P = 0.0049; rs880481: Allele A > G, chi2 = 10.3945, df = 1, P = 0.0013; Genotype, chi2 = 16.8049, df = 2, P = 0.0002). In addition, we constructed three-locus haplotypes to test their association with schizophrenia. The globe chi-squared test for haplotype analysis showed a significant association (chi2 = 66.38, df = 7, P < 0.000001). These results suggested that the FZD3 gene might be involved in the predisposition to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | J Neural Transm (Vienna) 2005 Feb 112: 303-7 |
| PMID | 15657645 |
| Title | Association study of the frizzled-3 (FZD3) gene with schizophrenia and mood disorders. |
| Abstract | Two research groups have recently reported a significant association between schizophrenia and genetic variants of Frizzled-3 (FZD3) gene. We examined a possible association in a Japanese sample of schizophrenia, bipolar disorder, unipolar depression and controls with four single nucleotide polymorphisms (SNPs), tested in previous reports. We failed to find significant association in the four SNPs or haplotype analysis. The FZD3 gene might not play a role in conferring susceptibility to major psychosis in our sample. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Psychiatry Res 2006 Jun 143: 1-11 |
| PMID | 16707163 |
| Title | Investigation of genetic association between human Frizzled homolog 3 gene (FZD3) and schizophrenia: results in a Korean population and evidence from meta-analysis. |
| Abstract | The neurodevelopmental hypothesis offers a promising approach through which to explore the pathogenesis of schizophrenia. Human Frizzled-3 protein is one of the major components of the Wnt signaling pathway and plays a crucial role in regulating early neurodevelopmental processes. Therefore, the human Frizzled homolog 3 (FZD3) gene, which encodes this protein, may be an excellent candidate gene for association studies of schizophrenia. To replicate the previously reported positive association between FZD3 and schizophrenia in Han Chinese and Japanese populations, we genotyped two single nucleotide polymorphism (SNP) markers of FZD3 in 241 unrelated schizophrenic patients and 192 control subjects. Fisher's exact test was used to compare the genotypic and allelic frequencies in the two groups. In addition, to integrate and evaluate the accumulated evidence published to date, we performed a meta-analysis on the published data, including our own. No evidence was found to support the association between either of the investigated SNP markers and schizophrenia in a Korean population. Moreover, the meta-analytic result did not support the association between several commonly investigated markers in FZD3 and schizophrenia. Failure to replicate previous positive association results could reflect various theoretical factors. Therefore, other sources of error have to be ruled out before coming to a conclusion. In the case of FZD3, it seems that repeated failures to replicate the original results by several independent research groups combine to provide evidence against an association between FZD3 and schizophrenia. Other candidate genes involved in early neurodevelopmental processes may deserve further investigation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Psychiatry Res 2006 Jun 143: 1-11 |
| PMID | 16707163 |
| Title | Investigation of genetic association between human Frizzled homolog 3 gene (FZD3) and schizophrenia: results in a Korean population and evidence from meta-analysis. |
| Abstract | The neurodevelopmental hypothesis offers a promising approach through which to explore the pathogenesis of schizophrenia. Human Frizzled-3 protein is one of the major components of the Wnt signaling pathway and plays a crucial role in regulating early neurodevelopmental processes. Therefore, the human Frizzled homolog 3 (FZD3) gene, which encodes this protein, may be an excellent candidate gene for association studies of schizophrenia. To replicate the previously reported positive association between FZD3 and schizophrenia in Han Chinese and Japanese populations, we genotyped two single nucleotide polymorphism (SNP) markers of FZD3 in 241 unrelated schizophrenic patients and 192 control subjects. Fisher's exact test was used to compare the genotypic and allelic frequencies in the two groups. In addition, to integrate and evaluate the accumulated evidence published to date, we performed a meta-analysis on the published data, including our own. No evidence was found to support the association between either of the investigated SNP markers and schizophrenia in a Korean population. Moreover, the meta-analytic result did not support the association between several commonly investigated markers in FZD3 and schizophrenia. Failure to replicate previous positive association results could reflect various theoretical factors. Therefore, other sources of error have to be ruled out before coming to a conclusion. In the case of FZD3, it seems that repeated failures to replicate the original results by several independent research groups combine to provide evidence against an association between FZD3 and schizophrenia. Other candidate genes involved in early neurodevelopmental processes may deserve further investigation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | J. Neural Transm. Suppl. 2007 -1 -1: 297-301 |
| PMID | 17982906 |
| Title | FZD3 is not a risk gene for schizophrenia: a case-control study in a Caucasian sample. |
| Abstract | Polymorphisms in the human frizzeled-3 (FZD3) gene have been associated with schizophrenia in an Asian population sample. However, this finding could not be confirmed in subsequent studies investigating other populations. Here we attempted to replicate this finding in a sample of 192 German chronically ill schizophrenic subjects. Three single nucleotide polymorphisms in the FZD3 gene have been genotyped by primer extension and MALDI-TOF measurement. Subsequently, associations for single markers as well as haplotypes were tested. In German patients, neither single markers nor haplotypes in FZD3 were associated with schizophrenia. Further exploratory analyses using a different diagnostic approach did also not yield significant results. FZD3 is unlikely to play a role in the genetic predisposition towards schizophrenia in the Caucasian population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | J. Neural Transm. Suppl. 2007 -1 -1: 297-301 |
| PMID | 17982906 |
| Title | FZD3 is not a risk gene for schizophrenia: a case-control study in a Caucasian sample. |
| Abstract | Polymorphisms in the human frizzeled-3 (FZD3) gene have been associated with schizophrenia in an Asian population sample. However, this finding could not be confirmed in subsequent studies investigating other populations. Here we attempted to replicate this finding in a sample of 192 German chronically ill schizophrenic subjects. Three single nucleotide polymorphisms in the FZD3 gene have been genotyped by primer extension and MALDI-TOF measurement. Subsequently, associations for single markers as well as haplotypes were tested. In German patients, neither single markers nor haplotypes in FZD3 were associated with schizophrenia. Further exploratory analyses using a different diagnostic approach did also not yield significant results. FZD3 is unlikely to play a role in the genetic predisposition towards schizophrenia in the Caucasian population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | J. Hum. Genet. 2008 -1 53: 739-46 |
| PMID | 18584117 |
| Title | Two-stage designs to identify the effects of SNP combinations on complex diseases. |
| Abstract | The genetic basis of complex diseases is expected to be highly heterogeneous, with many disease genes, where each gene by itself has only a small effect. Based on the nonlinear contributions of disease genes across the genome to complex diseases, we introduce the concept of single nucleotide polymorphism (SNP) synergistic blocks. A two-stage approach is applied to detect the genetic association of synergistic blocks with a disease. In the first stage, synergistic blocks associated with a complex disease are identified by clustering SNP patterns and choosing blocks within a cluster that minimize a diversity criterion. In the second stage, a logistic regression model is given for a synergistic block. Using simulated case-control data, we demonstrate that our method has reasonable power to identify gene-gene interactions. To further evaluate the performance of our method, we apply our method to 17 loci of four candidate genes for paranoid schizophrenia in a Chinese population. Five synergistic blocks are found to be associated with schizophrenia, three of which are negatively associated (odds ratio, OR < 0.3, P < 0.05), while the others are positively associated (OR > 2.0, P < 0.05). The mathematical models of these five synergistic blocks are presented. The results suggest that there may be interactive effects for schizophrenia among variants of the genes neuregulin 1 (NRG1, 8p22-p11), G72 (13q34), the regulator of G-protein signaling-4 (RGS4, 1q21-q22) and frizzled 3 (FZD3, 8p21). Using synergistic blocks, we can reduce the dimensionality in a multi-locus association analysis, and evaluate the sizes of interactive effects among multiple disease genes on complex phenotypes. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Behav Brain Funct 2008 -1 4: 37 |
| PMID | 18702828 |
| Title | The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population. |
| Abstract | Frizzled 3 (FZD3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia. Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls. A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis. Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Behav Brain Funct 2008 -1 4: 37 |
| PMID | 18702828 |
| Title | The Frizzled 3 gene is associated with methamphetamine psychosis in the Japanese population. |
| Abstract | Frizzled 3 (FZD3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia. Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls. A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis. Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | Mol. Psychiatry 2009 Jun 14: 563-89 |
| PMID | 19204725 |
| Title | Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. |
| Abstract | Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 18 | Neurosci. Lett. 2011 Nov 505: 196-9 |
| PMID | 22027177 |
| Title | Association study of the frizzled 3 gene with Chinese Va schizophrenia. |
| Abstract | Significant association of the FZD3 gene with schizophrenia in Chinese Han population had been reported previously, however, this finding could not be confirmed in subsequent studies investigating other populations. To understand the role of the FZD3 gene in schizophrenia further, here we attempted to replicate this finding in Chinese Va schizophrenic subjects which is one of the ethnic minorities in China. Five single nucleotide polymorphisms in the FZD3 gene had been genotyped by the polymerase chain reaction-based restriction fragment length polymorphism (RFLP) analysis based on the previous schizophrenic studies in 81 Va schizophrenic patients and 210 Va healthy subjects. Subsequently, associations for single markers as well as haplotypes were tested. There was a significant difference between patients and controls in the frequencies of the genotype or allele in rs2241802. Haplotype analyses revealed significant differences in patients and control subjects at rs2241802-rs2323019-rs352203 (global ?(2)=176.23, the degree of freedom=7, permutation p<0.0001). There were still the same significant differences for A-G-C and G-A-T haplotypes between the two groups after Bonferroni's correction. The present and previous findings indicated that genetic variants of the FZD3 gene may affect susceptibility to schizophrenia in Chinese Han and Va populations. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 19 | Neurosci. Lett. 2011 Nov 505: 196-9 |
| PMID | 22027177 |
| Title | Association study of the frizzled 3 gene with Chinese Va schizophrenia. |
| Abstract | Significant association of the FZD3 gene with schizophrenia in Chinese Han population had been reported previously, however, this finding could not be confirmed in subsequent studies investigating other populations. To understand the role of the FZD3 gene in schizophrenia further, here we attempted to replicate this finding in Chinese Va schizophrenic subjects which is one of the ethnic minorities in China. Five single nucleotide polymorphisms in the FZD3 gene had been genotyped by the polymerase chain reaction-based restriction fragment length polymorphism (RFLP) analysis based on the previous schizophrenic studies in 81 Va schizophrenic patients and 210 Va healthy subjects. Subsequently, associations for single markers as well as haplotypes were tested. There was a significant difference between patients and controls in the frequencies of the genotype or allele in rs2241802. Haplotype analyses revealed significant differences in patients and control subjects at rs2241802-rs2323019-rs352203 (global ?(2)=176.23, the degree of freedom=7, permutation p<0.0001). There were still the same significant differences for A-G-C and G-A-T haplotypes between the two groups after Bonferroni's correction. The present and previous findings indicated that genetic variants of the FZD3 gene may affect susceptibility to schizophrenia in Chinese Han and Va populations. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 20 | J. Psychopharmacol. (Oxford) 2012 Sep 26: 1218-30 |
| PMID | 22767372 |
| Title | A gene expression and systems pathway analysis of the effects of clozapine compared to haloperidol in the mouse brain implicates susceptibility genes for schizophrenia. |
| Abstract | Clozapine has markedly superior clinical properties compared to other antipsychotic drugs but the side effects of agranulocytosis, weight gain and diabetes limit its use. The reason why clozapine is more effective is not well understood. We studied messenger RNA (mRNA) gene expression in the mouse brain to identify pathways changed by clozapine compared to those changed by haloperidol so that we could identify which changes were specific to clozapine. Data interpretation was performed using an over-representation analysis (ORA) of gene ontology (GO), pathways and gene-by-gene differences. Clozapine significantly changed gene expression in pathways related to neuronal growth and differentiation to a greater extent than haloperidol; including the microtubule-associated protein kinase (MAPK) signalling and GO terms related to axonogenesis and neuroblast proliferation. Several genes implicated genetically or functionally in schizophrenia such as frizzled homolog 3 (FZD3), U2AF homology motif kinase 1 (UHMK1), pericentriolar material 1 (PCM1) and brain-derived neurotrophic factor (BDNF) were changed by clozapine but not by haloperidol. Furthermore, when compared to untreated controls clozapine specifically regulated transcripts related to the glutamate system, microtubule function, presynaptic proteins and pathways associated with synaptic transmission such as clathrin cage assembly. Compared to untreated controls haloperidol modulated expression of neurotoxic and apoptotic responses such as NF-kappa B and caspase pathways, whilst clozapine did not. Pathways involving lipid and carbohydrate metabolism and appetite regulation were also more affected by clozapine than by haloperidol. |
| SCZ Keywords | schizophrenia, schizophrenic |