Genes Immun. 2010 Jun 10. [Epub ahead of print]
Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis
Jamieson SE, Peixoto-Rangel AL, Hargrave AC, Roubaix LA, Mui EJ, Boulter NR, Miller EN, Fuller SJ, Wiley JS, Castellucci L, Boyer K, Peixe RG, Kirisits MJ, Elias LD, 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 LM, McLeod R, Blackwell JM.
 Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK  Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Subiaco, Western Australia, Australia.
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; 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
PMID: 20535134 [PubMed - as supplied by publisher]