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EVIDENCE FOR ASSOCIATIONS BETWEEN THE PURINERGIC RECEPTOR P2X7 (P2RX7) AND TOXOPLASMOSIS
Author
Jamieson, Sarra E.
Rangel, Alba Lucinia Peixoto
Hargrave, Aubrey C.
Roubaix, Lee-Anne de
Mui, Ernest J.
Boulter, Nicola R.
Miller, E. Nancy
Fuller, Stephen J.
Wiley, James S.
Castellucci, Léa
Boyer, Kenneth
Peixe, Ricardo Guerra
Kirisits, Michael J.
Elias, Liliani de Souza
Coyne, Jessica J.
Oliveira, Rodrigo Correa de
Sautter, Mari
Smith, Nicholas C.
Lees, Michael P.
Swisher, Charles N.
Heydemann, Peter
Noble, A. Gwendolyn
Patel, Dushyant
Bardo, Dianna
Burrowes, Delilah
McLone, David
Roizen, Nancy
Withers, Shawn
Oliveira, Lilian Maria Garcia Bahia de
McLeod, Rima
Blackwell, Jenefer M.
Rangel, Alba Lucinia Peixoto
Hargrave, Aubrey C.
Roubaix, Lee-Anne de
Mui, Ernest J.
Boulter, Nicola R.
Miller, E. Nancy
Fuller, Stephen J.
Wiley, James S.
Castellucci, Léa
Boyer, Kenneth
Peixe, Ricardo Guerra
Kirisits, Michael J.
Elias, Liliani de Souza
Coyne, Jessica J.
Oliveira, Rodrigo Correa de
Sautter, Mari
Smith, Nicholas C.
Lees, Michael P.
Swisher, Charles N.
Heydemann, Peter
Noble, A. Gwendolyn
Patel, Dushyant
Bardo, Dianna
Burrowes, Delilah
McLone, David
Roizen, Nancy
Withers, Shawn
Oliveira, Lilian Maria Garcia Bahia de
McLeod, Rima
Blackwell, Jenefer M.
Affilliation
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK/The University of Western Australia.Telethon Institute for Child Health Research. Centre for Child Health Research. Subiaco, WA, Australia.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK/ Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics/Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics/Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Technology. Institute for the Biotechnology of Infectious Diseases. Sydney, NSW, Australia.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK.
University of Sydney. Nepean Hospital. Nepean Clinical School. Penrith, NSW, Australia.
University of Sydney. Nepean Hospital. Nepean Clinical School. Penrith, NSW, Australia.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK / Federal University of Bahia. Salvador, Brazil.
Rush University Medical Center. Department of Pediatrics. Division of Pediatric Infectious Diseases. Chicago, Illinois, USA.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brazil
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brazil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Technology, Sydney. Institute for the Biotechnology of Infectious Diseases. NSW, Australia.
University of Technology, Sydney. Institute for the Biotechnology of Infectious Diseases. NSW, Australia.
Northwestern Children’s Hospital. Department of Pediatric Neurology. Chicago Illinois, USA.
Rush University Medical Center. Division of Pediatric Infectious Diseases. Department of Pediatrics. Chicago, Illinois, USA.
Departments of Ophthalmology, Medicine, Pediatrics, Committees on Immunology, Molecular Medicine, and Genetics Institute of Genomics and Systems Biology, and The College, University of Chicago, and Michael Reese Hospital and Medical Center, Chicago, Illinois, USA/ Department of Pediatric Neurology Northwestern Children’s Hospital, Chicago Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Department of Pediatric Neurology Northwestern Children’s Hospital, Chicago Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brazil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK/The University of Western Australia. Telethon Institute for Child Health Research. Centre for Child Health Research. Subiaco, WA, Australia.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK/ Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics/Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics/Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Technology. Institute for the Biotechnology of Infectious Diseases. Sydney, NSW, Australia.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK.
University of Sydney. Nepean Hospital. Nepean Clinical School. Penrith, NSW, Australia.
University of Sydney. Nepean Hospital. Nepean Clinical School. Penrith, NSW, Australia.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK / Federal University of Bahia. Salvador, Brazil.
Rush University Medical Center. Department of Pediatrics. Division of Pediatric Infectious Diseases. Chicago, Illinois, USA.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brazil
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brazil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Technology, Sydney. Institute for the Biotechnology of Infectious Diseases. NSW, Australia.
University of Technology, Sydney. Institute for the Biotechnology of Infectious Diseases. NSW, Australia.
Northwestern Children’s Hospital. Department of Pediatric Neurology. Chicago Illinois, USA.
Rush University Medical Center. Division of Pediatric Infectious Diseases. Department of Pediatrics. Chicago, Illinois, USA.
Departments of Ophthalmology, Medicine, Pediatrics, Committees on Immunology, Molecular Medicine, and Genetics Institute of Genomics and Systems Biology, and The College, University of Chicago, and Michael Reese Hospital and Medical Center, Chicago, Illinois, USA/ Department of Pediatric Neurology Northwestern Children’s Hospital, Chicago Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Department of Pediatric Neurology Northwestern Children’s Hospital, Chicago Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
Universidade Estadual do Norte Fluminense Darcy Ribeiro. Campos dos Goytacazes, RJ, Brazil.
Committees on Immunology, Molecular Medicine. Departments of Ophthalmology, Medicine, Pediatrics / Genetics Institute of Genomics and Systems Biology/The College University of Chicago/Michael Reese Hospital and Medical Center, Chicago, Illinois, USA.
University of Cambridge School of Clinical Medicine. Cambridge Institute for Medical Research and Department of Medicine. Cambridge, UK/The University of Western Australia. Telethon Institute for Child Health Research. Centre for Child Health Research. Subiaco, WA, Australia.
Abstract
Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus, and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong pro-inflammatory responses. Ligation of ATP by purinergic receptor P2X7, encoded by P2RX7, stimulates pro-inflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X7 plays a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z scores ±2.429; P= 0.015) between the derived C(+)G(−) allele (f= 0.68; OR= 2.06; 95% CI: 1.14–3.75) at SNP rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical sub-groups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0 to 4.25; 0.004<P<0.009) when hydrocephalus was removed from the analysis. Association with toxoplasmic retinochoroiditis was replicated (FBAT Z scores ±3.089; P= 0.002) in a small family-based study (60 families; 68 affected offspring) of acquired infection in Brazil, where the ancestral T(+) allele (f= 0.296) at SNP rs1718119 was strongly protective (OR= 0.27; 95% CI: 0.09–0.80)
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