Journal
GENES AND IMMUNITY
Volume 11, Issue 5, Pages 374-383Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2010.31
Keywords
toxoplasmosis; genetic polymorphisms; purinergic receptor P2X(7); North America; Brazil
Categories
Funding
- NIH [16945 01-20, 27530 01-20, 4328 01-11, 071319-01]
- FDA [RFA 8-86 01-2]
- CAPES [BEX 2371/06-05]
- CNPq [151950/2008-3, 558876/2008-0]
- FAPERJ [E-26/112045/2008]
- Australian Research Council [DP0666515]
- Australian Research Council [DP0666515] Funding Source: Australian Research Council
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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 P2RX(7), 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 P2RX(7) 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 <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). Genes and Immunity (2010) 11, 374-383; doi: 10.1038/gene.2010.31; published online 10 June 2010
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