title: Expression of immune genes on chromosome 6p21.3-22.1 in schizophrenia.
abstract: Schizophrenia is a common mental illness with a large genetic component. Three genome-wide association studies have implicated the major histocompatibility complex gene region on chromosome 6p21.3-22.1 in schizophrenia. In addition, nicotine, which is commonly abused in schizophrenia, affects the expression of central nervous system immune genes. Messenger RNA levels for genes in the 6p21.3-22.1 region were measured in human postmortem hippocampus of 89 subjects. The effects of schizophrenia diagnosis, smoking and systemic inflammatory illness were compared. Cell-specific expression patterns for the class I major histocompatibility complex gene HLA-A were explored utilizing in situ hybridization. Expression of five genes was altered in schizophrenic subjects. Messenger RNA levels for the class I major histocompatibility complex antigen HLA-B were increased in schizophrenic nonsmokers, while levels for smokers were indistinguishable from those of controls. β2 microglobulin, HLA-A and Notch4 were all expressed in a pattern where inflammatory illness was associated with increased expression in controls but not in subjects with schizophrenia. Schizophrenia was also associated with increased expression of Butyrophilin 2A2. HLA-A was expressed in glutamatergic and GABAergic neurons in the dentate gyrus, hilus, and the stratum pyramidale of the CA1-CA4 regions of the hippocampus, but not in astrocytes. In conclusion, the expression of genes from the major histocompatibility complex region of chromosome 6 with likely roles in synaptic development is altered in schizophrenia. There were also significant interactions between schizophrenia diagnosis and both inflammatory illness and smoking.
authors: Department of Psychiatry, University of Colorado Denver, Anschutz Medical Campus, Colorado 80045, USA. melissa.sinkus@ucdenver.edu
authors: Melissa L
authors: ML
authors: Sinkus
authors: Catherine E
authors: CE
authors: Adams
authors: Judith
authors: J
authors: Logel
authors: Robert
authors: R
authors: Freedman
authors: Sherry
authors: S
authors: Leonard
mesh_terms: D002896:Chromosomes, Human, Pair 6 / Q000235:genetics* / Q000276:immunology*; D015342:DNA Probes; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D005805:Genes, MHC Class I / Q000235:genetics; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000235:genetics*; D017403:In Situ Hybridization; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000276:immunology*; D012907:Smoking / Q000235:genetics / Q000276:immunology; D014015:Tissue Banks
chemical_list: D015342:DNA Probes; D015234:HLA-A Antigens; D012313:RNA
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