Mycobacterium tuberculosis co-existence with humans: making an imprint on the macrophage P2X7 receptor gene?

Abstract

The development of tuberculosis (TB) infection in humans depends on the mycobacterial strain and the human host, and is multigenically controlled in both. ATP ligation of P2X(7) receptors expressed on human macrophages infected with mycobacteria induces cell death and subsequent loss of intracellular bacterial viability. This study analysed the allelic distribution of two single-nucleotide polymorphisms (SNPs) in the P2RX7 gene in the Slavic population of the St Petersburg area of Russia. Analysis of the -762 C/T P2RX7 promoter SNP revealed no significant association between pulmonary TB patients and control subjects (3x2 chi(2)=3.2, 1 d.f., P=0.2). The -762C allele was highly and almost equally represented in both groups in this study (68.2 % in patients and 69.3 % in controls). This result differs strikingly from a Gambian study where this allele was found in only 7 and 12 % of pulmonary TB patients and controls, respectively [Li, C. M., Campbell, S. J., Kumararatne, D. S., Bellamy, R., Ruwende, C., McAdam, K. P. W. J., Hill, A. V. S. & Lammas, D. A. (2002). J Infect Dis 186, 1458-1462]. In contrast, the frequency of the C allele at position 1513 in exon 13, resulting in a loss of P2X(7) function, was significantly higher among pulmonary TB patients in this study (P=0.02). Thus, analysis of the P2X(7) receptor gene in the Russian Slavic population showed that the 1513C allele, acting dominantly, is a possible risk factor for clinical TB, whereas the -762 P2RX7 polymorphism did not appear to be associated with human susceptibility to TB.