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)

Schizophrenia (SCZ) is a severe neuropsychiatric disorder with a genetic component. The major inhibitory GABA-(gamma-aminobutyric acid) ergic system may be involved. The GABA type B receptor 1 (GABBR1) gene has been localized to 6p21.3, a region linked to SCZ. We therefore investigated five polymorphisms (A-7265G, C10497G, Ser-491-Ser-T1473C, Phe-659-Phe-T1977C, and 3'-UTR A33795G substitutions) in the GABBR1 gene in a sample of 101 DSM-IV SCZ probands and their families, 150 unrelated affected individuals matched with 150 healthy controls, using the transmission disequilibrium test (TDT) and case-control analysis. We did not observe biased transmission of alleles in any of the polymorphisms individually and haplotypes within the gene to SCZ probands. However, a weak significant difference was observed in the A-7265G polymorphism between the allelic frequency (chi2 = 4.310, P = 0.038) and a trend was observed between the genotype frequency (chi2 = 4.970, 2 df, P = 0.083) of SCZ individuals and controls. Further investigations of the role of GABBR1 in SCZ are warranted.
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PMID:Possible association between the gamma-aminobutyric acid type B receptor 1 (GABBR1) gene and schizophrenia. 1582 Apr 24

The synaptosomal-associated protein of 25 kDa (SNAP-25) is an essential component of the core complex that mediates presynaptic vesicle trafficking. Thus, SNAP-25 is directly involved in the release of neurotransmitters. Quantitative alterations of SNAP-25 expression have been reported in brain regions and cerebrospinal fluid (CSF) of schizophrenics and in haloperidol treated rats. This observed altered expression may be influenced by genetic variants of SNAP-25. We hypothesized that polymorphisms of the SNAP-25 gene (sites DdeI, MnlI and TaiI in the 3'UTR) are associated with antipsychotic drug response and induced weight gain. A sample of 59 patients with prior suboptimal response to antipsychotic treatment and diagnosed with DSM-IV schizophrenia or schizoaffective disorder was examined. Patients were administered clozapine, haloperidol, olanzapine or risperidone for up to 14 weeks. Clinical response was defined as the difference between the baseline and the endpoint total scores on the Positive and Negative Syndrome Scale (PANSS). Weight was assessed at baseline and at study endpoint. ANOVA revealed that the MnlI and TaiI polymorphisms were associated with response (F[2,53] = 4.57, p = 0.01 and F[2,52] = 3.53, p = 0.03) and with weight gain (F[2,52] = 4.28, p = 0.01 and F[2,51] = 3.38, p = 0.04). When covariates were included, the MnlI polymorphism remained significantly associated with changes of PANSS scores, but not with weight gain. The DdeI polymorphism was not associated with response or weight gain. These findings suggest that SNAP-25 gene variants affect clinical response in patients with prior poor response to antipsychotics. Weight changes do not seem to be associated with polymorphism of the SNAP-25 gene, however, replication in independent samples is warranted.
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PMID:The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. 1582 21

The TRAR4 gene locates in SCZD5 (MIM 603175), which a number of studies have linked with schizophrenia. One recent study suggested that three TRAR4 variants (M1: rs4305745, P=0.0014; M2: rs6903874, P=0.0026; M3: rs6937506, P=0.0052) in the 3'-UTR were associated with schizophrenia. To replicate these findings, we conducted a family-based association study within a sample of 235 Chinese Han trios. However, we didn't find significant evidence of preferential transmission of the three variants across all the trios (all P values>0.2). Thus, we conclude that TRAR4 is not a major or independent determinant in the occurrence of schizophrenia in the Chinese Han population.
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PMID:Failure to find association between TRAR4 and schizophrenia in the Chinese Han population. 1607 87

Recessive mutations of the potassium chloride co-transporter 3 gene ( SLC12A6 , KCC3 ) cause severe peripheral neuropathy frequently associated with agenesis of the corpus callosum and psychoses (ACCPN). SLC12A6 is localized on chromosome 15q14, a region where linkage to schizophrenia and bipolar disorder has previously been shown. Mutation analysis of SLC12A6 was carried out by direct sequencing of PCR-generated DNA fragments in two affected members of a multiplex family, and three non-affected individuals. A case-control study was performed to assess association of variants with bipolar disorder and schizophrenia in a large sample. Several variants including two rare single nucleotide polymorphisms (G/A, G/A) in the promoter and 5'-UTR, and a thymidine insertion in intron 4 were found. The two G variants and the insertion variant were co-inherited with chromosome 15-related schizophrenia in a large family that strongly supports the region on chromosome 15q14-15 between markers D15S144 and D15S132. Furthermore, they are in linkage disequilibrium with each other, and significantly associated with bipolar disorder in a case-control study. Our data strongly suggest that rare variants of SLC12A6 may represent risk factors for bipolar disorder.
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PMID:Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder. 1609 36

The NR2B protein is a critical structural and functional subunit of the NMDA glutamate receptor. The glutamate neurotransmitter system has been implicated in psychosis and schizophrenia, and so we looked for genetic association and measured gene expression in human DNA and brain samples, respectively, of the GRIN2B gene that codes for the NR2B protein. We tested three genetic polymorphisms: G-200T (5'UTR), A5806C and T5988C (both 3'UTR) in 180 matched schizophrenia case-control pairs, 86 schizophrenia nuclear family trios, and 318 bipolar disorder trios (of which 158 probands had psychotic symptoms). We measured brain GRIN2B mRNA levels in schizophrenia, bipolar disorder and unaffected controls (n = 35 each). We detected genetic association between the G-200T marker and schizophrenia (p = 0.002), between T5988C and bipolar disorder (p = 0.02), and between A5806C and bipolar disorder with psychotic symptoms (p = 0.0038). The T-C-C haplotype was transmitted more frequently with bipolar disorder, but less often with schizophrenia, while the G-C-T haplotype was transmitted more often in schizophrenia. Significant differences were found in overall haplotype frequencies between schizophrenia cases and controls (p = 0.005). GRIN2B expression levels in schizophrenia, bipolar disorder and controls were not significantly different. The genetic findings suggest a role for GRIN2B in schizophrenia and bipolar disorder.
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PMID:N-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels. 1654 38

A large body of evidence suggests that suicidal behavior is associated with altered noradrenergic neurotransmission. Norepinephrine is degraded by monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). Our hypothesis is that the genes encoding MAOA and COMT might contain genetic variants conferring increased risk for suicidal behavior in schizophrenia and that both genes may interact each other. In order to test this hypothesis, we genotyped the promoter VNTR polymorphism in the MAOA gene and three COMT polymorphisms: -287A>G, Val/Met and 3'UTR C Ins/Del in a cohort of 270 schizophrenics in which 92 attempted suicide. No association between suicide attempt and the MAOA VNTR (P = 0.382), Val108/158Met (P = 0.788) or -287A>G (P = 0.420) polymorphisms was found, however, a slight significant finding was found for 3'UTR polymorphism (P = 0.050). Haplotype analysis for COMT gene revealed no association between suicide attempts and haplotype distribution (P = 0.451). As we tested for epistasis between MAOA VNTR and COMT Val/Met, we found no significant interaction in conferring risk for suicide attempts (P = 0.545). These results suggest that epistasis between MAOA and COMT genes may not influence suicidal behavior in patients with schizophrenia.
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PMID:Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia. 1672 19

The dopamine hypothesis of schizophrenia proposes an inherited or acquired presynaptic hyperactivity of dopaminergic neurons. The human dopamine transporter gene (hSLC6A3; hDAT) represents one major mechanism for the termination of dopaminergic neurotransmission. This study examines the degree of genetic association of the 5'-untranslated region (5'-UTR) of the hSLC6A3 to schizophrenia in a family-based association design. Five single nucleotide polymorphisms (SNPs) derived by a previous systematic mutation scan approximately 1.2 kb of the 5'-UTR of the hSLC6A3 locus were genotyped for transmission disequilibrium between 82 index cases (56 males) with schizophrenia and their biological parents. We observed no preferential transmission of alleles from heterozygous parents to affected offspring. Five estimated haplotypes accounted for a frequency of 90% in the index cases, and were identical in cases and non-transmitted parental control haplotypes. Distinct five-locus-genotypes accumulated in schizophrenia compared to parental controls at P-value 0.0038 with odds-ratio of 2.02 (95% CI 0.99-4.14). In conclusion, our present findings support the genetic involvement of distinct hSLC6A3 genotypes in schizophrenia. We propose replication in extended samples and examination of the functional relevance of the associated genotypes on human dopamine transporter expression.
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PMID:Family-based study of markers at the 5'-flanking region of the human dopamine transporter gene reveals potential association with schizophrenic psychoses. 1678 97

The cannabinoid receptor 1 gene (CNR1) has been associated with addictive disorders and schizophrenia in different studies. We have compared the frequencies of the alleles for the 3'-UTR CNR1 microsatellite in a sample of 113 Spanish schizophrenic patients, including 68 with comorbid substance abuse, and 111 healthy controls. We report that the frequency of the allele 4 of this microsatellite is significantly lower in schizophrenia patients when compared with controls (chi(2) = 7.858; df 1; P = 0.005). No differences have been found with respect to substance abuse.Thus, the allele 4 represents, in our sample, a protective factor against schizophrenia (odds ratio 0.468, 95% confidence interval (CI) 0.27-0.79). The population attributable genetic risk for the allele 4 absence is 30% (95% CI = 17-41%) and the attributable risk for the allele 4 absence in those with schizophrenia is 53% (95% CI = 20-73%). Our results suggest that, independent of substance abuse, differences in the cannabinoid system function could be involved in the vulnerability to schizophrenia in Spanish population.
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PMID:(AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. 1678 67

Multiple lines of evidence suggest that schizophrenia results from aberrant neurodevelopment. The neurogenin1 gene (neurog1) consists of a single 1,666 bp exon that encodes a basic helix-loop-helix (bHLH) transcription factor that causes neuronal differentiation and induces cortical and glutamatergic differentiation programs. Because of its function and its location in 5q31.1, which has been linked to schizophrenia in multiple samples, we tested it for association with the disorder. We sequenced neurog1 in 25 affected subjects from the Irish Study of High-Density Schizophrenia Families. We observed a 5'-UTR SNP at position -60, already present in databases as rs8192558, and tested it along with rs2344485, rs8192559, and rs2344484. Narrow, intermediate, and broad diagnostic definitions were used. The major alleles of rs8192558 and rs2344484 were over-transmitted to affected subjects using both Pedigree Disequilibrium Test (PDT) (0.01 < or = P < or = 0.06) and FBAT (0.02 < or = P < or = 0.07). A haplotype consisting of the major alleles of all four SNPs was significantly over-transmitted in FBAT to the broad definition (P = 0.049), with trend significance to the narrow and intermediate definitions, and with trend significance in PDT. In confirmatory tests using 657 cases and 411 controls, this haplotype was slightly but not significantly over-represented in cases (81% vs. 77%, P = 0.21). These results, along with a priori evidence for the involvement of neurog1 in neurodevelopment, suggest that variants in neurog1 might have a small effect on susceptibility to schizophrenia. This gene should be tested in additional and larger samples.
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PMID:Association between the 5q31.1 gene neurogenin1 and schizophrenia. 1704

Synaptogyrin 1 gene (SYNGR1) is considered as a positional candidate gene for schizophrenia because of its location at chromosome 22q13, a region linked to schizophrenia, and its reduced expression in postmortem brain of patients with schizophrenia. Additionally, genetic studies also reported association of SYNGR1 is with schizophrenia and bipolar disorder in southern India. Prompted by these findings, we were interested to know if SYNGR1 is also associated with schizophrenia in our population. Therefore, we systematically searched for SYNGR1 mutations in a cohort of Han Chinese patients from Taiwan. Four single nucleotide polymorphisms (SNPs) were identified, including three at the putative core promoter region (g.-673A>C, g.-377G>A and g.-318G>T) that are in strong linkage disequilibrium and one in intron 2 (IVS2-64C>G). Computer program predicts that g.-637A>C and g.318G>T may change transcription binding sites of AP-1 and TGT3, respectively. We further carried out SNP- and haplotype-based case-control association studies of these tress SNPs with schizophrenia. However, no association was detected between these SNPs and schizophrenia in our sample. Nevertheless, we identified several rare mutations in exon 6 of SYNGR1 gene in our patient cohort (n=497), including a 3-bp (AAC) in-frame insertion between codon 202 and 203 (P202_T203insN) in two patients, an A-to-G missense mutation (c.665A>G) at codon 222 (D222G) in one patient, a synonymous mutation (c.669C>T) at codon 223 (T223T) in one patient, and a C-to-T at 3' UTR of SYNGR1 (c.772C>T) in one patient. These are mutations were not found in 507 control subjects, suggesting further functional assays are warranted to verify their relevance to the pathogenesis of schizophrenia.
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PMID:Identification of rare mutations of synaptogyrin 1 gene in patients with schizophrenia. 1704 58


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