%0 Journal Article
%T Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders
%A C. J. Carter
%J Journal of Pathogens
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/965046
%X Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (multiple sclerosis), and autism ( ), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself. 1. Introduction The protozoan parasite Toxoplasma gondii (T. gondii) which causes toxoplasmosis, is primarily hosted not only in cats but also in mice, rabbits, dogs, farmyard and wild animals, and domestic fowl, and is transmissible to man [1¨C5]. It has been implicated in the pathogenesis of many diseases, most notably schizophrenia [6¨C8], but also with bipolar disorder [9] depression and suicide attempts [10]. There is also evidence from serological antibody studies that the parasite may be implicated in the aetiology of Alzheimer¡¯s and Parkinson¡¯s disease [11¨C13] and in certain epilepsies of unknown origin [14]. The parasite has also been implicated in a number of autoimmune disorders including antiphospholipid syndrome, cryoglobulinemia, ANCA-associated vasculitides, autoimmune thyroid diseases, systemic sclerosis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus, possibly related to host/pathogen antigen homology [15, 16]. It has already been noted that several schizophrenia susceptibility genes are related to the T. gondii life cycle, as well as to that of other pathogens implicated in this condition (cytomegalovirus, influenza, rubella, and herpes viruses) [17, 18] and that in
%U http://www.hindawi.com/journals/jpath/2013/965046/