Expression of immune genes on chromosome 6p21.3-22.1 in schizophrenia

Brain Behav Immun. 2013 Aug;32:51-62. doi: 10.1016/j.bbi.2013.01.087. Epub 2013 Feb 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 6 / genetics*
  • Chromosomes, Human, Pair 6 / immunology*
  • DNA Probes
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Profiling
  • Gene Expression Regulation / immunology*
  • Genes, MHC Class I / genetics
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism
  • Hippocampus / metabolism
  • Humans
  • Immunity / genetics*
  • In Situ Hybridization
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Schizophrenia / genetics*
  • Schizophrenia / immunology*
  • Smoking / genetics
  • Smoking / immunology
  • Tissue Banks


  • DNA Probes
  • HLA-A Antigens
  • RNA