Voltar
Artigo Acesso aberto Produção Nacional Revisado por pares
BIBTEX RIS

Evidence for associations between the purinergic receptor P2X7 (P2RX7) and toxoplasmosis

2010; Springer Nature; Volume: 11; Issue: 5 Linguagem: Inglês

10.1038/gene.2010.31

ISSN

1476-5470

Autores

Scott Jamieson, Alba Lucínia Peixoto Rangel, Aubrey Hargrave, L-A. de Roubaix, Ernest Mui, Nicky Boulter, E. Nancy Miller, Stephen J. Fuller, James S. Wiley, Léa Cristina Castellucci, K. M. Boyer, Ricardo Guerra Peixe, Michael J. Kirisits, Liliani de Souza Elias, Jessica J. Coyne, Rodrigo Corrêa‐Oliveira, Mari Sautter, Nicholas C. Smith, Michael P. Lees, Charles N. Swisher, Peter Heydemann, A. Gwendolyn Noble, Dushyant V. Patel, Dianna M.E. Bardo, Delilah Burrowes, David G. McLone, Nancy Roizen, Shawn Withers, Lilian M. G. Bahia‐Oliveira, Rima McLeod, Jenefer M. Blackwell,

Tópico(s)

Adenosine and Purinergic Signaling

Resumo

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 P2X7, encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X7 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; P=0.015) between the derived C(+)G(−) allele (f=0.68; OR=2.06; 95% CI: 1.14–3.75) at single-nucleotide polymorphism (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 subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0–4.25; 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).

Referência(s)