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)

The aim of the study is to validate the etiological role of KIAA0027/MLC1 in childhood-onset megalencephalic leukoencephalopathy with subcortical cysts (MLC) and in schizophrenia, particularly the catatonic subtype, which were reported to be allelic diseases. Among a series of five patients with MLC, four mutant alleles were detected: one case of compound heterozygosity for a splice site mutation and a six-base-pair in-frame deletion, one patient with a homozygous frameshifting insertion-deletion, and a further case heterozygous for a A157E substitution. A systematic mutation screening in 140 index cases with schizophrenia revealed 13 different single nucleotide polymorphisms (SNPs): one SNP in the 5'-UTR, seven SNPs in intronic regions, two synonymous codon variants (T52, Y199), and three coding variants. Two of them, C171F and N218K, were observed in controls at a significant frequency. The L309M variant that was previously supposed to be the causative factor for chromosome 22q(tel) linked-periodic catatonia was found nonsegregating in a further multiplex pedigree. Furthermore, a complicated 33-bp insertion/deletion polymorphism at the 5'-end of exon 11 of MLC1 was found at equal frequency among schizophrenic patients and controls. In summary, our study provides further evidence for allelic heterogeneity in megalencephalic leukoencephalopathy, excludes MLC1 as a susceptibility locus for schizophrenia, and thereby rules out that MLC and schizophrenia are allelic disorders.
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PMID:Sequence diversity of KIAA0027/MLC1: are megalencephalic leukoencephalopathy and schizophrenia allelic disorders? 1249 30

Association studies on gene polymorphisms of neurotransmitter systems have hypothesized an involvement of dopamine receptors in susceptibility to schizophrenia. However, structural and morphological abnormalities in different brain regions of schizophrenic patients support neurodevelopmental etiology for schizophrenia and neurotrophic factor genes could be candidates for genetic studies. The glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic and potential differentiation factor for dopaminergic systems. We have performed, in an Italian sample, an association study on 3' UTR (AGG)n repeat in GDNF gene. Our results have evidenced a difference in the allele frequencies between patients and controls (CLUMP (T1) chi2 = 17.365, df = 9, P = 0.043) and the (AGG)n > or = 15 alleles (Fisher Exact Test (two side) chi2 = 11.818, df = 1, P = 0.0003) were more present in the controls group. Similarity, the carriers of (AGG)n > or = 15 (OR = 0.176 95% CI: 0.060-0.520) were more present in the same group. These results support that the (AGG)n > or = 15 alleles could be protective factors against schizophrenia and thus they suggest a possible involvement of GDNF gene in the genetic liability to illness.
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PMID:3' UTR (AGG)n repeat of glial cell line-derived neurotrophic factor (GDNF) gene polymorphism in schizophrenia. 1500 93

Chromosome 22q12 is one of the most promising regions for harboring a risk gene for schizophrenia. We have reported significant linkage of intermediate phenotypes for schizophrenia with markers within or near the beta-adrenergic receptor kinase 2 (ADRBK2, or GRK3) gene, which is highly expressed in dopaminergic pathways in the central nervous system, and mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors (GPCRs). A polymorphism in the promoter region of the ADRBK2 was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of the ADRBK2 gene for mutations in 48 schizophrenia probands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in the 5'-UTR/promoter region, and 16 rare variants in exonic and flanking regions, were identified. Among them, the Cys208Ser variant was the only non-synonymous mutation. Cys208Ser was found in one family without cosegregation between the variant and schizophrenia. Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The present study indicates that the ADRBK2 gene is unlikely to contribute strongly to schizophrenia susceptibility in this set of families.
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PMID:Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families. 1500 33

The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which have been assumed to be a possible factor in the pathogenesis of schizophrenia. It has been reported that in humans, the expression of one member of the DRP family, DRP-2, is decreased in the brains of individuals with schizophrenia. In addition, the DRP-2 gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. The *2236T > C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with controls. The frequency of the *2236C allele was significantly higher in controls than in patients with schizophrenia (P = 0.0097) and patients with paranoid-type schizophrenia (P = 0.0083). These results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.
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PMID:[The human dihydropyrimidinase-related protein 2 (DRP-2) gene on chromosome 8p21 is associated with paranoid-type schizophrenia]. 1502 29

A well established model for the pathophysiology of schizophrenia postulates a role for the NMDA-mediated glutamate transmission. The human gene coding for the 2B subunit of the NMDA receptor (GRIN2B) is considered a candidate based on its selective expression in brain. To evaluate the hypothesis that GRIN2B acts as a major gene in determining susceptibility to schizophrenia, a case-control association study was performed. Five single nucleotide polymorphisms (SNPs) were genotyped in 188 Italian patients and 156 control subjects. The association study showed a marginally significant excess of homozygosity for the polymorphism located in the 3'UTR region (P = 0.04). No other difference in genotype and allele frequencies was found in schizophrenics as compared to the control series. The case-control study was also carried out on estimated haplotypes, confirming a trend for association (P = 0.04). These results suggest that GRIN2B variations might be linked with susceptibility to schizophrenia. Replication studies on larger samples are warranted to further test this hypothesis.
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PMID:Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia: a case-control study. 1521 26

Mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT) and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, putative mutations recently have been described in a few autistic patients and a boy with language disorder and schizophrenia. In this study, DNA samples from individuals with schizophrenia and other psychiatric diseases were scanned in order to explore whether the phenotypic spectrum of mutations in the MECP2 gene can extend beyond the traditional diagnoses of RTT in females and severe neonatal encephalopathy in males. The coding regions, adjacent splicing junctions, and highly conserved segments of the 3'-untranslated region (3'-UTR) were examined in 214 patients, including 106 with schizophrenia, 24 with autism, and 84 patients with other psychiatric diseases by detection of virtually all mutations-single strand conformation polymorphism (SSCP) (DOVAM-S). To our knowledge, this is the first analysis of variants in conserved regions of the 3'-UTR of this gene. A total of 5.2 kb per haploid gene was analyzed (1.5 Mb for 214 patients). A higher frequency of missense and 3'-UTR variants was found in autism. One missense and two 3'-UTR variants were found in 24 patients with autism versus one patient with a missense change in 144 ethnically similar individuals without autism (P = 0.009). These mutations suggest that a possible association between MECP2 mutations and autism may warrant further study.
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PMID:MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. 1521 31

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) mediates a multitude of central nervous functions by activating 5-HT receptor subtypes. A dysfunction of serotonergic neurotransmission is considered to play a major role in the pathophysiology of complex neuropsychiatric disorders. In our study, a mutation screen of the serotonin receptor gene HTR3B was carried out to explore a putative contribution to the etiology of bipolar affective disorder (BPAD) and schizophrenia (SZ). Screening of 49 patients suffering from BPAD, 78 patients with SZ and 62 control individuals revealed eleven sequence variations including a 3 bp deletion within the 5'UTR (5' untranslated region), four exonic and five intronic SNPs as well as a point mutation in the 3'UTR of HTR3B. Four of these sequence variations have not been described previously. Statistical computation rated most variants as probably non-disease related polymorphisms. However, IVS6 + 31C > T, IVS6 + 40C > A, and 1386T > C were solely detected in bipolar affective patients and in none of the controls. Interestingly, we observed a significant underrepresentation of the 3 bp deletion -100_-102delAAG in an extended sample of 162 bipolar affected patients compared to controls (allele-wise: 8% vs. 15%, P = 0.006, OR = 0.49, 95% CI: 0.3-0.82; genotype-wise: 15,5% vs. 29,0%, P = 0.005, OR = 0.45, 95% CI: 0.26-0.77). We suggest that this deletion may influence translational efficiency, thereby possibly affecting the development of bipolar affective disease.
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PMID:Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients. 1538 65

Attention deficit hyperactivity disorder (ADHD) is a highly heritable and common disorder thought to arise, in part, from alterations in dopamine function. NR4A2, or Nurr1, is an orphan nuclear receptor implicated in the development of dopaminergic cells of the ventral tegmental area (VTA) and the substantia nigra (SN). Dopaminergic cells of the VTA provide innervation to the prefrontal cortex, believed to be of major importance in the etiology of ADHD, suggesting that NR4A2 is a potential candidate gene for ADHD susceptibility. This study aimed to identify polymorphisms in NR4A2 and test their association to ADHD. Database analysis revealed a CA repeat polymorphism in the 3' UTR of NR4A2 that was confirmed by PCR. SSCP screening revealed a common DeltaC polymorphism, 254 bp 5' to the transcriptional start site. These polymorphisms were tested for an association with ADHD in both a case control study of individuals from the Milwaukee Longitudinal Study of ADHD (103 cases and 66 controls), and in 35 families composed of trios or affected sib pairs (ASP) with ADHD. Functional effects of the promoter polymorphism were tested in vitro. The non-deleted allele was significantly more active in undifferentiated SK-N-MC cells compared to differentiated SK-N-MC and HeLa cells while a trend for increased activity for the DeltaC allele was observed in undifferentiated SK-N-MC cells. Identification of these polymorphisms may aid future candidate gene studies in disorders with altered dopamine signaling, such as schizophrenia Parkinson's disease and ADHD.
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PMID:Identification and characterization of human NR4A2 polymorphisms in attention deficit hyperactivity disorder. 1563 1

Low incidence of cancer in schizophrenia is one of the interesting puzzles in psychiatric field over decades. Analysis of genetic difference between schizophrenia and lung cancer might provide us with possible clues to understand molecular mechanisms of pathophysiology of schizophrenia. Epidermal growth factor (EGF), one of the potent growth promoting factors, has been studied for its roles in cancer development. EGF is also known to be involved in cognitive function. In order to analyze the genetic difference between schizophrenia and lung cancer, polymorphism of EGF gene was studied from 174 schizophrenia patients, 122 lung cancer patients and 132 controls in Korean population. Genotype frequency analysis of EGF gene (AluI restriction site, 5'-UTR, rs4444903) in the EGF gene was studied. The genotype and allele frequencies of the AluI polymorphism showed significant differences between schizophrenia and lung cancer patients [p<0.0001; p<0.0001, odds ratio (95% CI), 0.3690 (0.2600-0.5236)]. When compared with controls, schizophrenia patients showed no significant differences from controls in genotype and allele frequencies [p=0.5151; p=0.3516, odds ratio (95% CI), 0.8589 (0.6235-1.1830)]. However, lung cancer patients showed significant differences from controls in genotype and allele frequencies [p<0.0001; p<0.0001, odds ratio (95% CI), 2.3275 (1.6082-3.3687)]. These results indicate that schizophrenia is not associated with AluI polymorphism of EGF gene and EGF gene polymorphism is different between schizophrenia and lung cancer patients.
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PMID:Epidermal growth factor gene polymorphism is different between schizophrenia and lung cancer patients in Korean population. 1566 53

Neurocognitive deficits are recognized as a cardinal feature of schizophrenia. Atypical antipsychotics have high affinity for many neurotransmitter receptors. Among these receptors, antipsychotics are antagonists of adrenoceptors, and this pharmacological property has been postulated to be involved in the mechanism of action of antipsychotics. We tested the hypotheses that clinical response and cognitive improvement to antipsychotic treatment are associated with genetic variation in adrenergic alpha2C receptor (ADRA2C). Fifty-seven patients with chronic schizophrenia were prospectively assessed for clinical response to antipsychotic treatment. They were subsequently genotyped for a 21 bp insertion/deletion that we identified in the 3' untranslated region (3'UTR) of ADRA2C. With regard to clinical response and cognitive improvement to antipsychotics, there was no significant association observed for this polymorphism. Our results suggest that the novel polymorphism may not play a major role in antipsychotic response.
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PMID:Identification of a naturally occurring 21 bp deletion in alpha 2c noradrenergic receptor gene and cognitive correlates to antipsychotic treatment. 1568 53


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