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

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Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population. / Li, Cheuk; Campbell, S; Kumararatne, Dinakantha; Surprenant, A; Hill, AVS; Lammas, David.

In: The Journal of Infectious Diseases, Vol. 186, No. 10, 15.11.2002, p. 1458-1462.

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@article{df2582e6726f4de89c232196aa78072b,
title = "Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population",
abstract = "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.",
author = "Cheuk Li and S Campbell and Dinakantha Kumararatne and A Surprenant and AVS Hill and David Lammas",
year = "2002",
month = nov,
day = "15",
doi = "10.1086/344351",
language = "English",
volume = "186",
pages = "1458--1462",
journal = "The Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population

AU - Li, Cheuk

AU - Campbell, S

AU - Kumararatne, Dinakantha

AU - Surprenant, A

AU - Hill, AVS

AU - Lammas, David

PY - 2002/11/15

Y1 - 2002/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037110462&partnerID=8YFLogxK

U2 - 10.1086/344351

DO - 10.1086/344351

M3 - Article

C2 - 12404161

VL - 186

SP - 1458

EP - 1462

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

SN - 0022-1899

IS - 10

ER -