Association analysis of polymorphic CGG repeat in 5′ UTR of the reelin and VLDLR genes with schizophrenia

Akahane, Akihisa; Tanaka, Hiroshi; Nanko, Shinichiro

doi:10.1016/s0920-9964(01)00398-x

Cited by 34 publications

(23 citation statements)

References 22 publications

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“…An association of a single-nucleotide polymorphism at the 5' promoter region of the reelin gene with the schizophrenia phenotype has been reported, 27 but was not confirmed in a larger case-control association study. 28 The fact that reelin was most abnormal in the dentate gyrus granule cells is notable in light of other findings. Secretion of reelin by Cajal-Retzius interneurons in the marginal zone of the developing cortex is thought to act as a stop signal for migrating neurons.…”

Section: Discussionmentioning

confidence: 71%

Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium

et al. 2004

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Between 1997 and 2002, 48 data sets from the hippocampus were produced on samples from the Stanley Neuropathology Consortium. From these data sets, 224 total measures were available from the various subdivisions of the hippocampus. An integrative analysis of these measures was performed using a multivariate, nonparametric analysis of variance (ANOVA). ANOVA with correction for multiple comparisons indicated that parvalbumin-containing cells in CA2 were reduced in schizophrenia and bipolar disorder. In addition, reelin protein in the molecular layer of the dentate gyrus was decreased in schizophrenia, bipolar disorder, and depression at the trend level of statistical significance (P ¼ 0.065). These results strongly suggest a dysfunction of inhibitory GABA-ergic interneurons in severe mental illness. Without correction for multiple comparisons, 31 measures were abnormal in at least one disease, whereas 11 measures would be expected to appear abnormal by chance. Abnormal molecules included measures of synaptic density or neuronal plasticity (reelin, SNAP-25, BDNF, Complexin I and II), as well as parvalbumin, tyrosine receptor kinase A, glucocorticoid receptors, glutamate NR1 receptor subunits, serotonin 5HT2 A and 5HT1 B receptors, and dopamine D 5 receptors.

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Section: Discussionmentioning

confidence: 71%

Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium

et al. 2004

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“…To the best of our knowledge, the current study is the first SZ association study with such a large sample set, as well as the first using a gene-wide approach, when investigating variations in the large RELN gene, which spans 517.7 kbp and harbors 65 exons [Chen et al, 2002b]. Three previous publications have investigated if a polymorphic GGC repeat in the RELN 5 0 UTR [Akahane et al, 2002;Goldberger et al, 2005;Huang and Chen, 2006], reported to be associated with autism [Persico et al, 2001] and regulate RELN expression [Persico et al, 2006], is associated with SZ. All studies presented negative findings, but the sample sizes were small.…”

Section: Discussionmentioning

confidence: 99%

Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene

Kähler

Djurovic

Kulle

et al. 2008

American J of Med Genetics Pt B

106

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Several lines of evidence support the theory of schizophrenia (SZ) being a neurodevelopmental disorder. The structural, cytoarchitectural and functional brain abnormalities reported in patients with SZ, might be due to aberrant neuronal migration, since the final position of neurons affects neuronal function, morphology, and formation of synaptic connections. We have investigated the putative association between SZ and gene variants engaged in the neuronal migration process, by performing an association study on 839 cases and 1,473 controls of Scandinavian origin. Using a gene-wide approach, tagSNPs in 18 candidate genes have been genotyped, with gene products involved in the neuron-to-glial cell adhesion, interactions with the DISC1 protein and/or rearrangements of the cytoskeleton. Of the 289 markers tested, 19 markers located in genes MDGA1, RELN, ITGA3, DLX1, SPARCL1, and ASTN1, attained nominal significant P-values (P < 0.05) in either a genotypic or allelic association test. All of these genes, except transcription factor DLX1, are involved in the adhesion between neurons and radial glial cells. Eight markers obtained nominal significance in both tests, and were located in intronic or 3'UTR regions of adhesion molecule MDGA1 and previously reported SZ candidate RELN. The most significant result was attained for MDGA1 SNP rs9462341 (unadjusted association results: genotypic P = 0.00095; allelic P = 0.010). Several haplotypes within MDGA1, RELN, ITGA3, and ENAH were nominally significant. Further studies in independent samples are needed, including upcoming genome wide association study results, but our data suggest that MDGA1 is a new SZ susceptibility gene, and that altered neuronal migration is involved in SZ pathology.

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“…The gene product of disc1 is part of a microtubule motor complex, which is controlled by the Reelin and LIS1 signaling pathway (Assadi et al, 2003) and mutations in this gene result in abnormal development of the cortex (Kamiya et al, 2005). However, other genetic association screenings have yielded inconclusive results, including the searches for associations between reelin polymorphisms and schizophrenia (Akahane et al, 2002;Chen et al, 2002;Goldberger et al, 2005;Huang and Chen, 2006;Persico et al, 2006;Shifman et al, 2008;Gregorio et al, 2009). In contrast, a strong correlation between S-adenosyl-methionine (SAM), DNMT1, hypermethylation of the reelin promoter, and decreased Reelin expression in postmortem brains of subjects with schizophrenia has been reported Veldic et al, 2004;Abdolmaleky et al, 2005;Grayson et al, 2005;Guidotti et al, 2007;Ruzicka et al, 2007;Tochigi et al, 2008).…”

Section: Implications Of Altered Reelin Signaling For Neurological Anmentioning

confidence: 99%

Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases

Knuesel

2010

Progress in Neurobiology

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Association analysis of polymorphic CGG repeat in 5′ UTR of the reelin and VLDLR genes with schizophrenia

Cited by 34 publications

References 22 publications

Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium

Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium

Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene

Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases

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