Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.

Adenosine triphosphate (ATP) ligation of P2X(7) 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 antimycobacteria...

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Main Authors: Li, C, Campbell, S, Kumararatne, D, Bellamy, R, Ruwende, C, McAdam, K, Hill, A, Lammas, D
Format: Conference item
Published: 2002
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author Li, C
Campbell, S
Kumararatne, D
Bellamy, R
Ruwende, C
McAdam, K
Hill, A
Lammas, D
author_facet Li, C
Campbell, S
Kumararatne, D
Bellamy, R
Ruwende, C
McAdam, K
Hill, A
Lammas, D
author_sort Li, C
collection OXFORD
description Adenosine triphosphate (ATP) ligation of P2X(7) 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/P2X(7)-mediated host regulation of Mycobacterium tuberculosis infection.
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spelling oxford-uuid:0e778161-be76-4fc4-b065-79704e070f322022-03-26T09:46:02ZAssociation of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.Conference itemhttp://purl.org/coar/resource_type/c_5794uuid:0e778161-be76-4fc4-b065-79704e070f32Symplectic Elements at Oxford2002Li, CCampbell, SKumararatne, DBellamy, RRuwende, CMcAdam, KHill, ALammas, DAdenosine triphosphate (ATP) ligation of P2X(7) 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/P2X(7)-mediated host regulation of Mycobacterium tuberculosis infection.
spellingShingle Li, C
Campbell, S
Kumararatne, D
Bellamy, R
Ruwende, C
McAdam, K
Hill, A
Lammas, D
Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.
title Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.
title_full Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.
title_fullStr Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.
title_full_unstemmed Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.
title_short Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.
title_sort association of a polymorphism in the p2x7 gene with tuberculosis in a gambian population
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