Association between P2X7 Polymorphisms and Susceptibility to Tuberculosis: An Updated Meta-Analysis of Case-Control Studies

Abstract

Background and Objectives: Several studies inspected the impact of P2X7 polymorphisms on individual susceptibility to tuberculosis (TB), but the findings are still controversial and inconclusive. To achieve a more precise estimation, we conducted a meta-analysis of all eligible studies on the association between P2X7 polymorphisms and TB risk. Materials and Methods: Relevant studies were identified by searching the PubMed, Web of Science, Scopus and Google scholar databases up to November 2018. Twenty-four full-text articles were included in our meta-analysis. The strength of association between P2X7 polymorphisms and TB risk was evaluated by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models. Results: The findings of this meta-analysis revealed that the rs3751143 variant significantly increased the risk of TB in heterozygous codominant (OR = 1.44, 95%CI = 1.17−1.78, p = 0.0006, AC vs. AA), homozygous codominant (OR = 1.87, 95% CI = 1.40−2.49, p = 0.0004, CC vs. AA), dominant (OR = 1.50, 95% CI = 1.22−1.85, p = 0.0002, AC + CC vs. AA), recessive (OR = 1.61, 95% CI = 1.25−2.07, p = 0.001, CC vs. AC + AA), and allele (OR = 1.41, 95% CI = 1.19−1.67, p < 0.0001, C vs. A) genetic models. Stratified analysis showed that rs3751143 increased the risk of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in all genetic models. Furthermore, the rs3751143 increased risk of TB in the Asian population. The findings did not support an association between the rs2393799, rs1718119, rs208294, rs7958311, and rs2230911 polymorphisms of P2X7 and TB risk. Conclusions: The findings of this meta-analysis suggest that P2X7 rs3751143 polymorphism may play a role in susceptibility to TB in the Asian population. More well-designed studies are required to elucidate the exact role of P2X7 polymorphisms on TB development.

Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells

“…However, after pathogen clearance, only a few T cells remain as long-lived memory CD8 + T cells such as T RM or T SCM , which are critically dependent on cellular metabolism to regulate CD8 + T cell differentiation and memory formation (197)(198)(199)(200). For example, an essential requirement for the differentiation of T RM cells and T CM CD8 + T cells is purinergic receptor P2RX7 (201), which polymorphism on this gene plays a role in susceptibility to TB in the Asian population (202). In fact, non-lethal P2XR7 maintains mitochondrial homeostasis and TGF-b dependent programs of tissue residency by increasing AMPK activation compared with other tissue CD8 + T cells.…”

Genetic Variations of Angiotensinogen, Angiotensin Converting Enzyme, and Angiotensin Type 1 Receptor with the Risk of Pulmonary Tuberculosis

“…Only about 5-10% infected cases will develop active TB (Taheri et al, 2020;Wu et al, 2020), which proposes a key role of genetic factors in host immunity. Until now, various genes have been recognized as TB candidate genes and variants in these genes have been proposed as risk factors for the disease (Naderi et al, 2014;Taheri et al, 2019;Li et al, 2022).…”