Tumor necrosis factor-α -308 G/A polymorphism and risk of sepsis, septic shock, and mortality: an updated meta-analysis.
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ABSTRACT:
SUBMITTER: Wang H
PROVIDER: S-EPMC5706923 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSeveral case-control studies have been conducted to clarify the association between the tumor necrosis factor alpha (TNF-α) -G308A polymorphism and risk of osteoarthritis (OA); however, the results are inconsistent. This meta-analysis was performed to clarify this issue using all the available evidence.MethodsEligible articles were retrieved by searching PubMed, Web of science and Google scholar. The strength of the association between the TNF-α -G308A polymorphism and risk of OA was assessed by odds ratios (ORs) with the corresponding 95% confidence interval (CI) for each study.ResultsSeven studies were included in the meta-analysis, which included 983 OA cases and 1355 controls. The pooled analysis based on all included studies showed a significantly increased OA risk in the recessive genetic model analysis (OR = 11.08, 95% CI = 4.75-25.86, p < 0.001) and in the A allele vs. G allele analysis (OR = 2.30, 95% CI = 1.08-4.90). However, there was no statistical difference in the dominant genetic model analysis (OR = 2.45, 95% CI = 0.95-6.27, p = 0.06). Furthermore, we found that OA patients had a higher frequency of the AA genotype (OR = 10.49, 95% CI = 4.47-24.61) and GA genotype (OR = 1.78, 95% CI = 1.03-3.08) compared with the control population.ConclusionOur results suggested that the TNF-α -G308A polymorphism were associated with an increased risk of OA.
| S-EPMC4289255 | biostudies-literature
Project description:BackgroundMounting evidence has suggested that tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different.ObjectivesTo comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR.MethodData were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated.ResultsFor the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR (the OR [95% CI] of [GA vs. GG], [GA + AA] vs. GG, and [A vs. G] are 1.21 [1.04, 1.41], 1.20 [1.03, 1.39], and 1.14 [1.01, 1.30], respectively). And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was a mild correlation in the entire group (the OR [95% CI] of [GA vs. GG] is 1.55 [1.14, 2.11]), which was strengthened among the Asian population.ConclusionThe meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.
| S-EPMC8743915 | biostudies-literature
Project description:BACKGROUND:Tumor necrosis factor-alpha (TNF-?) is involved in cancer pathogenesis, and TNF-?-308G>A, a single-nucleotide polymorphism, is associated with cancer prognosis; however, different studies have reported inconsistent results. This meta-analysis aimed to determine the correlation between TNF-?-308G>A polymorphism and the survival of cancer patients. METHODS:PubMed, Web of Science, Embase, Wanfang database, VIP database, and China National Knowledge Infrastructure database were used to obtain articles on association between TNF-?-308G>A polymorphism and cancer survival, published until April 2018. A meta-analysis was carried out using Stata 12.0 software to determine the pooled hazard ratio (HR) and 95% confidence intervals (95% CI). Furthermore, publication bias was assessed, and sensitivity analysis was performed to validate the analysis. RESULTS:In total, 13 retrospective cohort studies including 2559 cancer patients were reviewed to estimate the association between TNF-?-308G>A polymorphism and overall survival (OS) of cancer patients. The pooled results suggested that within TNF-?-308G>A polymorphism, genotypes GA+AA/GG (HR?=?1.39, 95% CI: 0.90-2.14, P?<?.001, I?=?78.1%), GA/GG (HR?=?1.06, 95% CI: 0.83-1.36, P?=?.072, I?=?53.5%), and AA/AG+GG (HR?=?3.28, 95% CI: 0.92-11.72, P?=?.001, I?=?85.9%) were not associated with the OS of cancer patients. However, interestingly, the HR was greater for patients with the AA genotype than for those with the GG genotype, suggesting an association between TNF-?-308G>A polymorphism and OS among cancer patients (AA/GG, HR?=?2.16, 95% CI: 1.36-3.43, P?=?.281, I?=?21.5%). CONCLUSION:TNF-?-308G>A polymorphism affects the OS of cancer patients and is a potential therapeutic target for cancer.
| S-EPMC6250438 | biostudies-literature
Project description:More and more researches have been carried out on the association between the tumor necrosis factor-α (TNF-α) 308 G/A polymorphism and psoriasis, however, controversial results have emerged in these studies. This meta-analysis was performed to quantitatively clarify the relationship between TNF-α 308 G/A polymorphism and the risk of psoriasis in different populations. Databases of PubMed, Springer Link, Ovid, Chinese Wanfang Data Bases, Chinese National Knowledge Infrastructure and Chinese Biology Medicine were investigated until June 2019. The association between the TNF-α 308 G/A polymorphism and psoriasis was evaluated by calculating the pooled odds ratio (OR) and 95% confidence intervals (CIs). A total of 26 studies including 3657 patients and 3197 controls were screened out. In the overall population, the pooled results showed a reduced psoriasis risk with the TNF-α 308 G/A polymorphism (A vs G: OR = 0.77, 95% CI = 0.67-0.89; AA+GA vs GG: OR = 0.72, 95% CI = 0.61-0.86). In the subgroup analysis stratified by geographic locations, the TNF-α 308 G/A polymorphism was significantly associated with a reduced risk of psoriasis in Germany (A vs G: OR = 0.67, 95% CI = 0.57-0.78; AA+GA vs GG: OR = 0.62, 95% CI = 0.52-0.75), as well as in China (AA+GA vs GG: OR = 0.71, 95% CI = 0.52-0.98) and Poland (A vs G: OR = 0.61, 95% CI = 0.38-0.97; AA+GA vs GG: OR = 0.59, 95% CI = 0.35-0.99). This study indicated a significantly reduced psoriasis risk associated with the TNF-α 308 G/A polymorphism in Germans, as well as in Chinese and Poles populations compared with other populations. Ethnicity and geographic locations probably play a pivotal role in the genetic association of psoriasis.
| S-EPMC7676592 | biostudies-literature
Project description:UnlabelledEnvironmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (-251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP.ResultsThe TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25-9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease.ConclusionAn analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients.
| S-EPMC3946307 | biostudies-literature
Project description:PurposeManagement of sepsis in critically ill patients remains difficult and requires prolonged intensive care. Genetic testing has been proposed as a strategy to identify patients at risk for adverse outcome of critical illnesses. Therefore, we wished to determine the influence of heredity on predisposition to poor outcome and on duration of ventilator support of intensive care unit (ICU) patients.MethodsA study was conducted from July 2001 to December 2005 in heterogeneous population of patients from 12 US ICUs represented by the Genetic Predisposition to Severe Sepsis (GenPSS) archive. In 1057 Caucasian critically ill patients with SAPS II probability of survival of >0.2 in the US, six functional single nucleotide polymorphisms in relation to inflammatory cytokines and innate immunity (rs1800629, rs16944, rs1800795, rs1800871, rs2569190, and rs909253) were evaluated in terms of mortality and ventilator free days.ResultsThe AA homozygote of TNF(-308) (rs1800629) was most over-represented in the deceased patient group (P=0.015 with recessive model). The carriage of the TNF(-308)*AA genotype showed significantly higher odds ratio of 2.67(1.29-5.55) (P=0.008) after adjustment with the covariates. However, the presence of 1, 2, or 3 acute organ dysfunctions was larger prognostic factors for the adverse outcome (OR(95%CI)=2.98(2.00-4.45), 4.01(2.07-7.77), or 19.95(4.99-79.72), P<0.001 for all). Kaplan-Mayer plot on ventilator duration of TNF(-308)*AA patient significantly diverged from that of TNF(-308)*(GG+GA) ((AA v GG+GA), Adjusted HR(95%CI)=2.53(1.11-5.79) with Cox regression, P=0.028).ConclusionsTNF(-308)*AA is significantly associated with susceptibility to adverse outcome and to longer ventilator duration. Therefore, heredity likely affects both predisposition to ICU prognosis as well as the resource utilization.
| S-EPMC3570580 | biostudies-literature
Project description:Coronary artery disease (CAD) is the leading cause of death worldwide and remains a major health problem, providing the rationale for identification of molecular markers for detection of individuals at high risk of developing CAD. Tumor necrosis factor-α (TNF-α) plays a crucial role in the pathogenesis of CAD. We have therefore explored the association of TNF-α 308 (G/A) gene polymorphism in 903 individuals with/without CAD. TNF-α 308 gene polymorphism was analyzed in 903 subjects of whom 222 were healthy controls. Among the 681 patients who were investigated angiographically, 468 had ≧50% stenosis and 213 patients had <50% stenosis. Biochemical profiles (eg, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and CRP) were evaluated. Associations between TNF-α genotypes with biochemical and anthropometric characteristics were determined. The frequencies of TNF-α-AA or AG genotypes were significantly lower in patients classified as CAD patients with ≥ or <50% obstruction in at least one coronary artery, compared to the control group. We observed that CAD patients with ≥50% stenosis and with AA genotype were associated with higher risk of CAD with OR of 3.56 (95%CI: 1.02-12.41; P=.046) using multivariate analysis. Moreover, we found that TNF-α-308-AA genotype was associated with blood pressure and CRP level in CAD patients, compared to the wild type-genotype. Our data showed an association of TNF-α-308G/A polymorphism with CAD patients with ≥50% obstruction, supporting the need for further investigations on the role of TNF-α-308G/A polymorphism with hypertension.
| S-EPMC6817255 | biostudies-literature
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
| S-EPMC5538252 | biostudies-other
Project description:Many studies have investigated the association between Tumor necrosis factor-α-308 G>A (rs1800629) and the risk of esophageal cancer. However, their results are inconsistent. Therefore, we performed a meta-analysis of available data to investigate any possible association between this polymorphism and esophageal cancer risk. We searched PubMed, EMBASE, Web of Science, and the CNKI database for articles published up to 2016. Crude and adjusted odds ratio with 95% confidence intervals were calculated using fixed or random effects models. We used a dominant model (GA+AA vs GG), a recessive model (AA vs GG+GA), an over-dominant model (GG+AA vs GA), and allele frequency (G vs A) to identify any association. Eleven studies with 5617 participants were included in the meta-analysis. Our results suggest that TNF-α-308 G>A (rs1800629) is not significantly associated with a risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma. For genetic association studies, negative results of meta-analysis have a high level of evidence, and these results are important in this era of high-throughput sequencing-based precision medicine.
| S-EPMC5346759 | biostudies-literature
Project description:Uncovering risk factors playing roles in the severity of Coronavirus disease 2019 (Covid-19) are important for understanding pathoimmunology of the disease caused by severe acute respiratory syndrome Coronavirus 2 (SARS CoV-2). Genetic variations in innate immune genes have been found to be associated with Covid-19 infections. A single-nucleotide polymorphism (SNP) in a promoter region of tumor necrosis factor alpha (TNF-α) gene, TNF-α -308G>A, increases expression of TNF-α protein against infectious diseases leading to immune dysregulations and organ damage. This study aims to discover associations between TNF-α -308G>A SNP and Covid-19 infection. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping a general Kurdish population and Covid-19 patients. The homozygous mutant (AA) genotype was found to be rare in the current studied population. Interestingly, the heterozygous (GA) genotype was significantly (p value = 0.0342) higher in the Covid-19 patients than the general population. This suggests that TNF-α -308G>A SNP might be associated with Covid-19 infections. Further studies with larger sample sizes focusing on different ethnic populations are recommended.
| S-EPMC9102518 | biostudies-literature