Association of a Polymorphism in the P2X7 Gene with Tuberculosis in a Gambian Population
Adenosine triphosphate (ATP) ligation of P2X7 receptors expressed on human macrophages that are infected with mycobacteria induces cell death and subsequent loss of intracellular bacterial viability. Marked heterogeneity observed in cell donor ATP responsiveness suggests that this antimycobacterial...
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Published in | The Journal of infectious diseases Vol. 186; no. 10; pp. 1458 - 1462 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Chicago, IL
The University of Chicago Press
15.11.2002
University of Chicago Press |
Subjects | |
Online Access | Get full text |
ISSN | 0022-1899 1537-6613 |
DOI | 10.1086/344351 |
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Summary: | Adenosine triphosphate (ATP) ligation of P2X7 receptors expressed on human macrophages that are infected with mycobacteria induces cell death and subsequent loss of intracellular bacterial viability. Marked heterogeneity observed in cell donor ATP responsiveness suggests that this antimycobacterial mechanism may be genetically regulated. Five single-nucleotide polymorphisms (SNPs) previously identified in a putative 1.8-kb promoter region upstream of P2RX7 exon 1 were screened for associations with clinical tuberculosis. The frequencies of these promoter SNPs and a polymorphism in P2RX7 exon 13 at position 1513 were compared among >300 Gambian patients with tuberculosis and >160 ethnically matched control subjects by sequence-specific oligonucleotide hybridization and ligation detection reaction analysis. A significant protective association against tuberculosis was found for 1 promoter SNP, at nucleotide position −762 (odds ratio [OR] for variant C allele, 0.70; 95% confidence interval [CI], 0.54–0.89; P=.003; OR for CC genotype, 0.545; 95% CI, 0.318–0.934; P=.027). This association supports a role for ATP/P2X7-mediated host regulation of Mycobacterium tuberculosis infection |
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Bibliography: | ark:/67375/HXZ-8N7S7GK4-F istex:5091CC1D144B6A5A4069F4B967CE0FA2D3818F8F ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-1899 1537-6613 |
DOI: | 10.1086/344351 |