Association of a Polymorphism in the P2X7 Gene with Tuberculosis in a Gambian Population

• Published in: The Journal of infectious diseases Vol. 186; no. 10; pp. 1458 - 1462
• Main Authors: Li, Cheuk M., Campbell, Sarah J., Kumararatne, Dinakantha S., Bellamy, Richard, Ruwende, Cyril, McAdam, Keith P. W. J., Hill, Adrian V. S., Lammas, David A.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.11.2002; University of Chicago Press
• Subjects: Adult; Bacterial diseases; Biological and medical sciences; Female; Gambia; Genetic Predisposition to Disease; Human bacterial diseases; Humans; Infectious diseases; Male; Medical sciences; Polymorphism, Genetic; Receptors, Purinergic P2 - genetics; Receptors, Purinergic P2X7; Tropical medicine; Tuberculosis - ethnology; Tuberculosis - genetics; Tuberculosis and atypical mycobacterial infections; Gambia; Africa; Human; Host agent relation; Mycobacterial infection; Genetic determinism; Infection; Tuberculosis; Gene; Mycobacterium tuberculosis; Mycobacteriales; Purinergic receptor; Bacteriosis; Mycobacteriaceae; Bacteria; Actinomycetes; Polymorphism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/344351

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