P2X7 Gene Polymorphisms and Risk Assessment for Pulmonary Tuberculosis in Asian Indians

Venkatasubramanian, Sambasivan; Murthy, K. J. R.; Reddy, Ravindra; Vijayalakshimi, Valluri; Hasan, Qurratulain

doi:10.1155/2010/843729

Cited by 41 publications

(33 citation statements)

References 19 publications

(39 reference statements)

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“…We found that the -762 T allele is a risk factor for PTB in our study population. In contrast to our findings, Sambasivan et al (2010) found a significant difference between PTB patients and controls for the -762 C allele and reported that the C allele is a risk factor for PTB in the Asian Indian population. Xiao et al (2009) found that the -762T/C variant of P2X7 was not significantly associated with TB in the Chinese Han population.…”

Section: Discussioncontrasting

confidence: 99%

Association of P2X7 gene polymorphisms with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran

Bahari

Hashemi²,

Taheri³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Susceptibility to tuberculosis may be influenced by variations in human genes. The P2X7 receptor is an ATP-gated cation channel expressed in immune cells, and it influences the release of proinflammatory cytokines from monocytes and macrophages. In the present study, we aimed to evaluate the impact of P2X7 gene rs2393799 (-762T/C) and rs1718119 (Thr348Ala) polymorphisms on patient susceptibility to pulmonary tuberculosis (PTB) in a sample of the Iranian population. This case-control study was performed using 150 PTB cases and 150 controls. P2X7 receptor polymorphisms were determined using tetra-amplification refractory mutation system-polymerase chain reaction. Genotype and allelic frequencies of the rs2393799 variant P2X7 gene polymorphisms in pulmonary tuberculosis within the P2X7 gene were significantly higher in the PTB patients than in the healthy controls. The genotypes were CC in 71, CT in 54, and TT in 25 PTB patients. The genotypes were CC in 104, CT in 40, and TT in 6 healthy controls. The results indicate a significant association between rs2393799 polymorphism of the P2X7 gene and susceptibility to PTB (CT vs CC: OR = 6.5, 95%CI = 2.5-16.9, P < 0.0001; TT vs CC: OR = 3.3, 95%CI = 1.2-8.9, P = 0.018; TC+TT vs CC: OR = 2.56, 95%CI = 1.59-4.12, P < 0.0001). The rs2393799 T allele is a risk factor for predisposition to PTB (OR = 2.53, 95%CI = 1.73-3.71, P < 0.0001). No association between the rs1718119 polymorphism and PTB was found. In conclusion, the rs2393799 polymorphism in the P2X7 gene may contribute to patient susceptibility to PTB in our study population.

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Section: Discussioncontrasting

confidence: 99%

Association of P2X7 gene polymorphisms with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran

Bahari

Hashemi²,

Taheri³

et al. 2013

Genet. Mol. Res.

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“…However, in their analysis, only males showed a signifi cant association between P2X7-762 T/C and TB. Our results were also similar to those observed in Indian populations, and are supported by a recent meta-analysis reporting subjects with the C allele at higher risk of developing TB [22,23].…”

Section: Discussionsupporting

confidence: 91%

“…Thus, sequence changes in this region may affect the activity of P2X7 receptor expression and alters its ability to regulate macrophage activity which helps in controlling TB infection [22]. Additional to 762 polymorphism, 1513 T to C allele frequency in the P2X7 gene were also investigated.…”

Section: Discussionmentioning

confidence: 99%

Association of IFN-γ and P2X7 Receptor Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients

Shamsi

Zolfaghari

Farnia

2016

Acta Microbiologica et Immunologica Hungarica

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Interferon-gamma (IFN-γ) and P2X7 receptor are crucial for host defence against mycobacterial infections. Recent studies have indicated that IFN-γ, IFN-γ receptor 1 (IFN-γR1) andP2X7 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis (TB). However, the relationship between IFN-γ and P2X7 polymorphism and TB susceptibility remains inconclusive in Iranian population. For this reason, single nucleotide polymorphisms (SNPs) in IFN-γ (G+2109A), IFN-γR1 (G-611A) and P2X7 genes (at -762, 1513 position) in patients (n = 100) were assessed using PCR-RFLP. Data were analysed with SPSS version 18. For the 2109 loci of IFN-γ gene, the frequency of mutant alleles between patients and controls were not statistically signifi cant. However, there was a signifi cant difference between the TB patient and controls for -611 alleles of IFN-γR1 (P = 0.01). Additionally, the frequency of P2X7 gene polymorphisms (SNP-762 and 1513) between patients and controls was statistically signifi cant. In conclusions, our study revealed a signifi cant association of IFN-γR1 and P2X7 genes polymorphisms with risk of developing TB in Iranian population.

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“…They found that a protective effect against tuberculosis was associated with a P2X 7 receptor promoter polymorphism at position −762, but the 1513 A>C polymorphism discussed above did not show any significant association. Interestingly, Sambasivan et al [42] found an association between development of clinical tuberculosis and the presence of the −762C or 1729T allele but not the 1513C allele in an Indian cohort, while Xiao et al [43] did not find an association between either the 1513C allele or the −762C allele and the development of pulmonary tuberculosis in a Chinese Han cohort. Overall, though, a recent meta-analysis of P2X 7 receptor gene polymorphism association studies revealed a strong association between the 1513 A>C polymorphism and susceptibility to tuberculosis [44].…”

Section: The P2x7 Receptor and Intracellular Bacteriamentioning

confidence: 97%

The Role of the P2X7 Receptor in Infectious Diseases

et al. 2011

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ATP is an extracellular signal for the immune system, particularly during an inflammatory response. It is sensed by the P2X7 receptor, the expression of which is upregulated by pro-inflammatory cytokines. Activation of the P2X7 receptor opens a cation-specific channel that alters the ionic environment of the cell, activating several pathways, including (i) the inflammasome, leading to production of IL-1β and IL-18; (ii) the stress-activated protein kinase pathway, resulting in apoptosis; (iii) the mitogen-activated protein kinase pathway, leading to generation of reactive oxygen and nitrogen intermediates; and (iv) phospholipase D, stimulating phagosome-lysosome fusion. The P2X7 receptor can initiate host mechanisms to remove pathogens, most particularly those that parasitise macrophages. At the same time, the P2X7 receptor may be subverted by pathogens to modulate host responses. Moreover, recent genetic studies have demonstrated significant associations between susceptibility or resistance to parasites and bacteria, and loss-of-function or gain-of-function polymorphisms in the P2X7 receptor, underscoring its importance in infectious disease.

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P2X7 Gene Polymorphisms and Risk Assessment for Pulmonary Tuberculosis in Asian Indians

Cited by 41 publications

References 19 publications

Association of P2X7 gene polymorphisms with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran

Association of P2X7 gene polymorphisms with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran

Association of IFN-γ and P2X7 Receptor Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients

The Role of the P2X7 Receptor in Infectious Diseases

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