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

Jamieson, S.E., Peixoto-Rangel, A.L., Hargrave, A.C., de Roubaix, L.-A., Mui, E.J., Boulter, N.R., Miller, E.N., Fuller, S.J., Wiley, J.S., Castellucci, L., Boyer, K., Peixe, R.G., Kirisits, M.J., de Souza Elias, L., Coyne, J.J., Correa-Oliveria, R., Sautter, M., Smith, N.C., Lees, M.P., Swisher, C.N., Heydemann, P., Nobel, A.G., Patel, D., Bardo, D., Burrowes, D., McLone, D., Roizen, N., Withers, S., Bahia-Oliveria, L.M.G., McLeod, R., and Blackwell, J.M. (2010) Evidence for associations between the purinergic receptor P2X₇ (P2RX7) and toxoplasmosis. Genes and Immunity, 11. pp. 374-383.

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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 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).

Item ID: 26373
Item Type: Article (Research - C1)
ISSN: 1476-5470
Keywords: toxoplasmosis; genetic polymorphisms; purinergic receptor P2X7; North America; Brazil
Date Deposited: 10 May 2013 06:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 90%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 Innate Immunity @ 10%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 40%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 20%
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