Apoptotic engulfment pathway and schizophrenia.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Apoptosis*; ATP-Binding Cassette Transporters/*physiology ; Adaptor Proteins, Signal Transducing/*physiology ; Membrane Proteins/*physiology ; Schizophrenia/*physiopathology; ATP Binding Cassette Transporter 1 ; Asian People ; China ; Ethnicity ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic Markers ; Genotype ; Germany ; Humans ; Ireland ; Schizophrenia/ethnology ; United States ; White People
    • Abstract:
      Background: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease.
      Methodology/principal Findings: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples.
      Conclusions/significance: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.
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    • Grant Information:
      R01 MH041953 United States MH NIMH NIH HHS; R01MH41953 United States MH NIMH NIH HHS
    • Accession Number:
      0 (ABCA1 protein, human)
      0 (ABCA7 protein, human)
      0 (ATP Binding Cassette Transporter 1)
      0 (ATP-Binding Cassette Transporters)
      0 (Adaptor Proteins, Signal Transducing)
      0 (GULP1 protein, human)
      0 (Genetic Markers)
      0 (MEGF10, human)
      0 (Membrane Proteins)
    • Publication Date:
      Date Created: 20090902 Date Completed: 20100201 Latest Revision: 20221207
    • Publication Date:
      20231215
    • Accession Number:
      PMC2731162
    • Accession Number:
      10.1371/journal.pone.0006875
    • Accession Number:
      19721717