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 phenomenon of anticipation has been demonstrated in several neuropsychiatric disorders and suggested for schizophrenia and bipolar affective disorder. Many conditions exhibiting anticipation have been shown to be caused by trinucleotide repeat (CAG/CTG) expansions. Some evidence suggests that these expansions also exist in individuals with schizophrenia and bipolar affective disorder. In this investigation, we analysed a polymorphic CAG repeat in the interleukin receptor gene (IL9R), mapped to the pseudoautosomal region Xq28 and Yq21 (a candidate region for schizophrenia and affective disorder). Two common alleles, differing by one repeat unit and two rare alleles were found in cases and controls. Allele frequencies of this repeat were investigated in Irish schizophrenic, bipolar disorder and ethnically matched control samples. We found no evidence of an increased frequency of larger CAG repeats in either the schizophrenic or bipolar affective disorder samples as a whole when compared to the controls. However, dividing the samples by sex demonstrated a significant association between bipolar affective disorder males and the larger allele (allele 2) (patients 54.8% vs controls 40.1%, chi2 = 6.7, P = 0.009). In addition, a decreased frequency of this allele has been observed in the female patients, but did not attain statistical significance (patients 37% vs controls 46%, chi2 = 2.1, P = 0.14). This provides preliminary evidence that this locus or a closely mapped DNA variant (in linkage disequilibrium with the CAG repeat) may be involved in the genetic susceptibility to bipolar affective disorder in males.
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PMID:Pseudoautosomal gene: possible association with bipolar males but not with schizophrenia. 1055 42

A growing body of research suggests the involvement of immune system factors in central nervous system development and in pathophysiology related to schizophrenia.(1,2) We therefore investigated the Tumor Necrosis Factor Receptor-II (TNF-RII), a TNFalpha receptor expressed in fetal brain, as a candidate disease gene for schizophrenia. We also investigated the relationship between TNF-RII and adult brain morphology. The study sample consisted of 140 probands diagnosed with schizophrenia or schizophreniform disorder, 197 parents of the probands (a subset of which formed 62 proband-parent trios), and 46 psychiatrically normal control subjects. A bi-allelic TNF-RII polymorphism was examined for evidence of association, with none being found between this polymorphism and schizophrenia. Subjects with schizophrenia homozygous for allele 1, however, had larger ventricles and smaller frontal lobes than subjects with at least one copy of allele 2. On follow-up testing, they also had an earlier, less variable age of onset for their illness. We found no support, therefore, for TNF-RII as a disease susceptibility gene for schizophrenia. The gene may, however, modify phenotypic aspects of the disease such as brain morphology and age of onset of illness.
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PMID:Tumor necrosis factor receptor-II: heritability and effect on brain morphology in schizophrenia. 1112 99

This study was undertaken to re-examine whether homozygosity for the Gly-9 variant (allele 2) of the dopamine D3 receptor gene (DRD3) is associated with increased risk for tardive dyskinesia (TD) in schizophrenic patients. Seventy-one antipsychotic-treated subjects with schizophrenia from Newcastle upon Tyne, UK, were genotyped for the presence of allele 1 (Ser-9) and allele 2 (Gly-9) of the dopamine D3 receptor (DRD3) Ser-9-Gly polymorphism. Among 32 patients with TD, 7 subjects (22 %) were homozygous for the Gly-9 variant (2-2 genotype), whereas 4 out of 39 patients (10 %) without TD had this genotype. The non-significant tendency in this sample towards an over-representation of allele 2 and the 2-2 genotype among schizophrenic patients with TD is in line with our initial report as well as recent studies by others, indicating that the Gly-9 allele of DRD3 may be a susceptibility factor for the development of TD in neuroleptic-treated individuals with schizophrenia. There are, however, some recent non-supportive reports, and since the trend in our present study failed to reach statistical significance, further studies on larger samples and future meta-analysis may be necessary to establish the role of the DRD3 in the pathogenesis of TD.
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PMID:Homozygosity for the Gly-9 variant of the dopamine D3 receptor and risk for tardive dyskinesia in schizophrenic patients. 1134 80

It has been established that cytokines play a critical role in the regulation of the CNS and recent studies have suggested that dysfunctions of both pro-inflammatory (IL-1beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-1RA and IL-10) cytokines could be involved in the pathophysiology of schizophrenia. Previous studies have reported that functional polymorphisms in some cytokines genes may have important regulatory effects on such system. Therefore, the aim of the present study was to explore the possible role of the IL-1beta -511C/T and IL-1RA (86bp)(n) repeats polymorphisms in schizophrenia. A case control association study comparing genotype and allele frequencies in 346 northen Italian subjects (169 schizophrenic patients and 177 unrelated healthy volunteers) was performed. The frequencies of IL-1beta -511C and IL-1RA allele 1 (86bp)(4) are significantly higher in schizophrenic patients compared to controls (IL-1beta -511 P=0.047; IL-1RA (86bp)(n) P=0.002). Moreover our data show a protective effect of the IL-1RA allele 2 (86bp)(2) against schizophrenia (OR=0.59 95%CI:0.388-0.910; P=0.016) and this effect is enhanced by the concomitant presence of IL-1beta -511T (OR=0.48 95%CI:0.30-0.76; P=0.002). Our findings support the hypothesis that genetically determined changes in IL-1 metabolism regulation may contribute to the pathogenesis of schizophrenia confirming a role of IL-1 gene cluster in disease susceptibility.
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PMID:Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia. 1456 76

Interleukin-1beta (IL-1beta), as well as other cytokines, has been classically implicated in the pathophysiology of major psychiatric disorders such as schizophrenia and major depression, and recent studies have implicated the IL-1beta gene and schizophrenia. Nevertheless, new approaches to this complex phenotype are necessary to clarify the risk conferred by this gene, either to the disorder or to its clinical manifestations. The aim of the present study was to explore the effect of a genetic polymorphism of the promoter region of the IL-1beta gene, in schizophrenia defined with: (i) a categorical diagnosis and (ii) a multidimensional symptom approach. We studied 356 individuals from 89 nuclear families consisting of one affected individual and the unaffected father, mother, and sib, in a family-based association study design. We find a trend for biased transmission of allele 2 from heterozygous parents to affected offspring, categorically defined (P = 0.07). This tendency was not observed in the healthy offspring. Using a multidimensional symptom approach to the diagnosis, the association was confirmed in psychotic patients showing the depressive symptom-dimension (P = 0.02).
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PMID:Interleukin-1beta (IL-1beta) gene and increased risk for the depressive symptom-dimension in schizophrenia spectrum disorders. 1468 6

Hypoactivity of the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks is among the most consistent findings in schizophrenia. The biological factors contributing to this hypofrontality are only partially known. Previous reports have shown the influence of genes mapped to IL-1 cluster (i) in the risk to develop schizophrenia and (ii) on brain morphological abnormalities in these patients. Moreover, Interleukin-1beta (IL-1beta), encoded by IL-1B gene (IL-1 cluster, chromosome 2q13) has a key role in dopaminergic differentiation and dendrite growth in developing cortical neurons. The authors explored the role of a genetic functional polymorphism at IL-1B gene in relation to DLPFC activity. DLPFC (left and right) metabolic activity was measured in a sample of 19 DSM-IV diagnosed schizophrenic patients of Spanish origin using a procedure based on MRI/PET image fusion. During PET studies, subjects performed a contingent Continuous Performance Test aiming to activate DLPFC. Functional promoter polymorphism -511 C/T (rs16944) of IL-1B gene was genotyped in these patients. Those patients who were allele 2 (-511 T) carriers showed a lower metabolic activity in the left DLPFC with respect to patients homozygous for allele 1 (-511 C) (U = 16, z = -2.32, P = 0.02). Our results suggest that hypofrontality reported in some schizophrenic patients might be explained, at least in part, by this functional polymorphism at IL-1B gene. Genetic variants with influence on brain functionality may account for the neurocognitive heterogeneity observed in schizophrenic patients.
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PMID:Effect of interleukin-1beta gene functional polymorphism on dorsolateral prefrontal cortex activity in schizophrenic patients. 1751 Sep 51

Interleukin-1beta (IL-1beta) and neuregulin-1 (NRG-1) have an important role in development of the central nervous system. Several recent studies suggest that their genetic polymorphisms are associated with schizophrenia. We studied the effects of the IL-1beta gene (IL-1B) -511 and NRG-1 SNP8NRG221533 polymorphisms and their interactions on the risk and age of onset of schizophrenia in 113 Finnish schizophrenic patients and 393 healthy controls. The allele and genotype frequencies of IL-1B and NRG-1 did not differ between schizophrenic patients and healthy controls, but the risk of schizophrenia was more than 10 times higher (odds ratio 10.20, 95% CI 2.53-41.09, p = 0.001) among subjects with the IL-1B 2.2, NRG-1 CC genotypes compared to subjects with the IL-1B 2.2, NRG-1 T-allele carriage. There was also a trend for an association between the interaction between IL-1B and NRG-1 polymorphisms and the age at onset of schizophrenia (chi(2) = 2.80; df = 1; p = 0.09, log rank test). IL-1B-511 allele 1 homozygotes had a significantly higher age of onset than allele 2 carriers (mean age of onset 25.9 +/- 7.7 and 22.7 +/- 5.4 years, t-test: t = 2.46; p = 0.032). Our results suggest that there is an interaction between the IL-1B and NRG-1 genes in schizophrenia. In addition, the IL-1B-511 polymorphism seems to be associated with the age at onset of schizophrenia.
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PMID:Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia. 1790 98


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