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      A Meta-Analysis of P2X7 Gene-762T/C Polymorphism and Pulmonary Tuberculosis Susceptibility

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          Abstract

          Aim

          We performed a comprehensive meta-analysis to determine the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis susceptibility.

          Methodology

          Based on comprehensive searches of the PubMed, SCI, Elsevier, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis risk. Pooled odds ratio (ORs) and 95% confidence intervals (95%CIs) were calculated in random-effects model.

          Results

          A total of 2207 tuberculosis cases and 2220 controls in 8 case-control studies were included in this meta-analysis. Allele model (C vs. T: p = 0.15; OR = 0.83, 95% CI = 0.65–1.07), homozygous model (CC vs. TT: p = 0.23; OR = 0.73, 95% CI = 0.44 to 1.22), and heterozygous model (CT vs. TT: p = 0.57; OR = 0.92, 95% CI = 0.68 to 1.24) did not show increased risk of developing pulmonary tuberculosis. Similarly, dominant model (CC+CT vs. TT: p = 0.32; OR = 0.84, 95% CI = 0.59 to 1.19) and recessive model (CC vs. CT+TT: p = 0.08; OR = 0.77, 95% CI = 0.57 to 1.04) failed to show increased risk of developing pulmonary tuberculosis. Subgroup analysis by ethnicity did not detect any significant association between P2X7–762T/C polymorphism and pulmonary tuberculosis susceptibility.

          Conclusions

          P2X7 -762T/C gene polymorphism is not associated with pulmonary tuberculosis susceptibility.

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          Most cited references19

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          How meta-analysis increases statistical power.

          One of the most frequently cited reasons for conducting a meta-analysis is the increase in statistical power that it affords a reviewer. This article demonstrates that fixed-effects meta-analysis increases statistical power by reducing the standard error of the weighted average effect size (T.) and, in so doing, shrinks the confidence interval around T.. Small confidence intervals make it more likely for reviewers to detect nonzero population effects, thereby increasing statistical power. Smaller confidence intervals also represent increased precision of the estimated population effect size. Computational examples are provided for 3 effect-size indices: d (standardized mean difference), Pearson's r, and odds ratios. Random-effects meta-analyses also may show increased statistical power and a smaller standard error of the weighted average effect size. However, the authors demonstrate that increasing the number of studies in a random-effects meta-analysis does not always increase statistical power.
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            WHO's 2013 global report on tuberculosis: successes, threats, and opportunities.

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              Susceptibility to mycobacterial infections: the importance of host genetics.

              There is substantial evidence that host genetic factors are important in determining susceptibility to mycobacteria. Several different techniques have been used to identify the genes involved. Studies of an inbred strain of mice with increased susceptibility to mycobacteria, salmonella and leishmania infections led to the identification of the natural resistance-associated macrophage protein gene (Nramp1). Case-control studies have confirmed the importance of the human equivalent of this gene, NRAMP1, and have also suggested that the major histocompatibility complex and vitamin-D receptor genes may be involved in determining human susceptibility to mycobacteria. Studies of individuals with the rare condition of increased susceptibility to disseminated bacille Calmette-Guerin and other atypical mycobacterial infections have identified several abnormalities in the genes encoding the interferon gamma receptor (IFNgammaR) ligand binding chain, IFNgammaR signal transduction chain, IFNgamma signal transduction and activation of transcription-1, interleukin 12 receptor beta1 subunit and interleukin 12 p40 subunit. A genome-wide linkage study has been performed to identify genes exerting a major effect on tuberculosis susceptibility in the general population. Linkages were found to markers on chromosomes 15 and X. Studies to identify the genes responsible are in progress.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                8 May 2014
                : 9
                : 5
                : e96359
                Affiliations
                [1]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Key Laboratory of Respiratory Diseases, Ministry of Health, Wuhan, Hubei, China
                Tor Vergata University of Rome, Italy
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LY GZ. Performed the experiments: LY DC HS. Analyzed the data: LY DC HS. Contributed reagents/materials/analysis tools: XH KZ. Wrote the paper: LY GZ.

                Article
                PONE-D-13-53666
                10.1371/journal.pone.0096359
                4014486
                24810548
                24fcf2cb-bba6-4ba5-90db-9a840dd7eda9
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 December 2013
                : 5 April 2014
                Page count
                Pages: 7
                Funding
                This study was supported by National Natural Science Foundation of China Grant 81170022, and National Key Technology R&D Program of the 12th Five-year Development Plan 2012BAI05B01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Evolutionary Biology
                Population Genetics
                Genetic Polymorphism
                Genetics
                Genomics
                Genomic Medicine
                Genetic Counseling
                Population Biology
                Medicine and Health Sciences
                Clinical Genetics
                Epidemiology
                Genetic Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Public and Occupational Health
                Global Health
                Tropical Diseases
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Research Design
                Clinical Research Design

                Uncategorized
                Uncategorized

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