Evidence for associations between the purinergic receptor P2X 7 (P2RX7) and toxoplasmosis

Jamieson, SE; Peixoto-Rangel, AL; Hargrave, AC; Roubaix, LAD; Mui, EJ; Boulter, NR; Miller, EN; Fuller, SJ; Wiley, JS; Castellucci, L; Boyer, K; Peixe, RG; Kirisits, MJ; Elias, LDS; Coyne, JJ; Correa-Oliveira, R; Sautter, M; Smith, NC; Lees, MP; Swisher, CN; Heydemann, P; Noble, AG; Patel, D; Bardo, D; Burrowes, D; McLone, D; Roizen, N; Withers, S; Bahia-Oliveira, LMG; McLeod, R; Blackwell, JM

Evidence for associations between the purinergic receptor P2X 7 (P2RX7) and toxoplasmosis

Jamieson, SE Peixoto-Rangel, AL Hargrave, AC Roubaix, LAD Mui, EJ Boulter, NR Miller, EN Fuller, SJ Wiley, JS Castellucci, L Boyer, K Peixe, RG Kirisits, MJ Elias, LDS Coyne, JJ Correa-Oliveira, R Sautter, M Smith, NC

Lees, MP Swisher, CN Heydemann, P Noble, AG Patel, D Bardo, D Burrowes, D McLone, D Roizen, N Withers, S Bahia-Oliveira, LMG McLeod, R Blackwell, JM

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Publication Type:: Journal Article
Citation:: Genes and Immunity, 2010, 11 (5), pp. 374 - 383
Issue Date:: 2010-07-01

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Field	Value	Language
dc.contributor.author	Jamieson, SE	en_US
dc.contributor.author	Peixoto-Rangel, AL	en_US
dc.contributor.author	Hargrave, AC	en_US
dc.contributor.author	Roubaix, LAD	en_US
dc.contributor.author	Mui, EJ	en_US
dc.contributor.author	Boulter, NR	en_US
dc.contributor.author	Miller, EN	en_US
dc.contributor.author	Fuller, SJ	en_US
dc.contributor.author	Wiley, JS	en_US
dc.contributor.author	Castellucci, L	en_US
dc.contributor.author	Boyer, K	en_US
dc.contributor.author	Peixe, RG	en_US
dc.contributor.author	Kirisits, MJ	en_US
dc.contributor.author	Elias, LDS	en_US
dc.contributor.author	Coyne, JJ	en_US
dc.contributor.author	Correa-Oliveira, R	en_US
dc.contributor.author	Sautter, M	en_US
dc.contributor.author	Smith, NC https://orcid.org/0000-0002-7467-1451	en_US
dc.contributor.author	Lees, MP	en_US
dc.contributor.author	Swisher, CN	en_US
dc.contributor.author	Heydemann, P	en_US
dc.contributor.author	Noble, AG	en_US
dc.contributor.author	Patel, D	en_US
dc.contributor.author	Bardo, D	en_US
dc.contributor.author	Burrowes, D	en_US
dc.contributor.author	McLone, D	en_US
dc.contributor.author	Roizen, N	en_US
dc.contributor.author	Withers, S	en_US
dc.contributor.author	Bahia-Oliveira, LMG	en_US
dc.contributor.author	McLeod, R	en_US
dc.contributor.author	Blackwell, JM	en_US
dc.date.issued	2010-07-01	en_US
dc.identifier.citation	Genes and Immunity, 2010, 11 (5), pp. 374 - 383	en_US
dc.identifier.issn	1466-4879	en_US
dc.identifier.uri	http://hdl.handle.net/10453/14900
dc.description.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 proinflammatory responses. Ligation of ATP by purinergic receptor P2X 7, encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X 7 has 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; P0.015) between the derived C()G() allele (f0.68; OR2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068TC; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR3.0-4.25; 0.004P0.009) when hydrocephalus was removed from the analysis. Association with toxoplasmic retinochoroiditis was replicated (FBAT Z-scores 3.089; P0.002) in a small family-based study (60 families; 68 affected offspring) of acquired infection in Brazil, where the ancestral T() allele (f0.296) at SNP rs1718119 was strongly protective (OR0.27; 95% CI: 0.09-0.80). © 2010 Macmillan Publishers Limited All rights reserved.	en_US
dc.relation.ispartof	Genes and Immunity	en_US
dc.relation.isbasedon	10.1038/gene.2010.31	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Toxoplasmosis, Congenital	en_US
dc.subject.mesh	Chorioretinitis	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Receptors, Purinergic P2	en_US
dc.subject.mesh	Logistic Models	en_US
dc.subject.mesh	Haplotypes	en_US
dc.subject.mesh	Inheritance Patterns	en_US
dc.subject.mesh	Linkage Disequilibrium	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Child, Preschool	en_US
dc.subject.mesh	North America	en_US
dc.subject.mesh	Brazil	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.subject.mesh	Receptors, Purinergic P2X7	en_US
dc.title	Evidence for associations between the purinergic receptor P2X 7 (P2RX7) and toxoplasmosis	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.citation.volume	11	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
dc.location.activity	ISI:000280150200002	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical Sciences
utslib.copyright.status	closed_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	11	en_US

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 proinflammatory responses. Ligation of ATP by purinergic receptor P2X 7, encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X 7 has 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; P0.015) between the derived C()G() allele (f0.68; OR2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068TC; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR3.0-4.25; 0.004P0.009) when hydrocephalus was removed from the analysis. Association with toxoplasmic retinochoroiditis was replicated (FBAT Z-scores 3.089; P0.002) in a small family-based study (60 families; 68 affected offspring) of acquired infection in Brazil, where the ancestral T() allele (f0.296) at SNP rs1718119 was strongly protective (OR0.27; 95% CI: 0.09-0.80). © 2010 Macmillan Publishers Limited All rights reserved.

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http://hdl.handle.net/10453/14900