Association Of TNF-α Research Articles

Genetically predicted inflammatory cytokine levels and risk of retinitis pigmentosa

ABSTRACT Purpose This study aims to estimate the potential causal relationship between genetically predicted levels of inflammatory cytokine and retinitis pigmentosa (RP) by performing Mendelian randomization (MR). Methods Single nucleotide polymorphisms (SNPs) were identified as instrumental variables (IVs) from publicly available genome-wide association study datasets. Inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were applied in this MR analysis. IVW and MR-Egger were used to confirm heterogeneity and pleiotropy of identified IVs. Leave-one-SNP-out analysis was used to identify SNPs with potential impact. Results IVW results revealed that elevated levels of Tumor Necrosis Factor Alpha (TNF-α), Macrophage Inflammatory Protein-1a (MIP1a), and Monokine Induced by Gamma Interferon (MIG) were associated with higher RP risk (OR = 2.358, p = 0.050; OR = 2.583, p = 0.013; OR = 1.851, p = 0.015), while elevated levels of Interleukin-16 (IL-16) were associated with reduced RP risk (OR = 0.723, p = 0.019). The results of heterogeneity and pleiotropy (p > 0.05) confirmed there was no pleiotropy and heterogeneity in our IVW analysis. The association of TNF-α, MIP1a, MIG and IL-16 with RP from sensitivity analyses using these two sets of restricted IVs remained stable. Conclusion Our study provides evidence of potential causal relationships between several circulating cytokine levels and RP. Elevated levels of TNF-α, MIP1a, and MIG are associated with a higher risk of RP, while elevated levels of IL-16 are associated with a lower risk of RP. These cytokines may be novel biomarkers and therapeutic targets for RP.

Association of TNFα and IL10 polymorphisms with pulmonary tuberculosis susceptibility in an admixed population from a high-burden region in Northeast Brazil

Association of TNFα and IL10 polymorphisms with pulmonary tuberculosis susceptibility in an admixed population from a high-burden region in Northeast Brazil

Association of TNF-α, IGF-1, and IGFBP-1 levels with the severity of osteopenia in mice with nonalcoholic fatty liver disease

BackgroundsNonalcoholic fatty liver disease (NAFLD) exhibits a close association with osteoporosis. This work aims to assess the potential effects of NAFLD on the progression of osteopenia in animal models.MethodsForty-eight C57BL/6 female mice were randomly divided to wild-type (WT) group and high-fat diet (HFD) group. The corresponding detections were performed after sacrifice at 16, 24 and 32 weeks, respectively.ResultsAt 16 weeks, an remarkable increase in body weight and lipid aggregation in the hepatocytes of HFD group was observed compared to the WT group, while the bone structure parameters showed no significant difference. At 24 weeks, the levels of TNF-α and IL-6 in NAFLD mice were significantly increased, while the level of osteoprotegerin mRNA in bone tissue was decreased, and the level of receptor activator of nuclear factor Kappa-B ligand mRNA was increased. Meanwhile, the function of osteoclasts was increased, and the bone microstructure parameters showed significant changes. At 32 weeks, in the HFD mice, the mRNA levels of insulin-like growth factor-1 (IGF-1), runt-related transcription factor 2, and osterix mRNA were reduced, while the insulin-like growth factor binding protein-1 (IGFBP-1) level was increased. Simultaneously, the osteoblast function was decreased, and the differences of bone structure parameters were more significant, showing obvious osteoporosis.ConclusionsThe bone loss in HFD mice is pronounced as NAFLD progresses, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles at the different stages of NAFLD in HFD.

The Association of TNFα -308 Polymorphism and TNFα serum level in a sample of Multiple Sclerosis Iraqi patients

Tumor necrosis factor-alpha TNF-α) is a pro-inflammatory cytokine that is involved in the pathogenesis of Multiple Sclerosis. The current study was designed to examine the association between TNF-α level and TNF-α gene polymorphisms in Multiple Sclerosis of Iraqi patients. Blood samples were collected from fifty Iraqi patients who suffered from Multiple Sclerosis (20 men and 30 women) with ages ranging between 23-54 years, and 50 healthy volunteers as a control group. The serum level of TNF-α was detected by using an Enzyme-Linked Immuno-sorbent assay (ELISA), and TNF-α-308 gene polymorphism was assessed by TaqMan Real-time Polymerase Chain Reaction (Taq-RT-PCR). The results of the estimation of TNF-α level showed high elevation in the patients’ group (4.88 ± 0.17 pg/ml) with a high significance difference (P≤0.01) as compared with the control group (2.96 ± 0.09 pg/ml). While detection of TNF-α-308 polymorphism in MS patients revealed that the wild genotype G/G was 3 (6.00%), heterogeneous genotype GA was 15 (30.00%). Homogeneous genotype AA was 32 (46.00%), while G allele frequency was 0.21 and A allele was 0.79 with significant difference (P≤ 0.005) and even as in control G/G genotype was 47 (94 %), GA genotype was 3 (6.00%), AA genotype was 0 (0.00%), G allele frequency was 0.97. A allele was 0.03 with significant difference (P≤ 0.01). The result revealed a significant difference between TNF-α-308 genotype and TNFα serum level in MS patients and control. Keywords: TNF-α-308, MS, ELISA, Taq-PCR.

Association of TNF-α (-308G/A) Gene Polymorphism with Changes in Circulating TNF-α Levels in Response to CPAP Treatment in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

We recently demonstrated that patients with coronary artery disease (CAD) and obstructive sleep apnea (OSA) carrying the tumor necrosis factor-alpha (TNF-α) A allele had increased circulating TNF-α levels compared with the ones carrying the TNF-α G allele. In the current study, we addressed the effect of TNF-α (-308G/A) gene polymorphism on circulating TNF-α levels following continuous positive airway pressure (CPAP) therapy. This study was a secondary analysis of the RICCADSA trial (NCT00519597) conducted in Sweden. CAD patients with OSA (apnea-hypopnea index) of ≥15 events/h and an Epworth Sleepiness Scale (ESS) score of <10 were randomized to CPAP or no-CPAP groups, and OSA patients with an ESS score of ≥10 were offered CPAP treatment. Blood samples were obtained at baseline and 12-month follow-up visits. TNF-α was measured by immunoassay (Luminex, R&D Systems). Genotyping of TNF-α-308G/A (single nucleotide polymorphism Rs1800629) was performed by polymerase chain reaction-restriction fragment length polymorphism. In all, 239 participants (206 men and 33 women; mean age 64.9 (SD 7.7) years) with polymorphism data and circulating levels of TNF-α at baseline and 1-year follow-up visits were included. The median circulating TNF-α values fell in both groups between baseline and 12 months with no significant within- or between-group differences. In a multivariate linear regression model, a significant change in circulating TNF-α levels from baseline across the genotypes from GA to GA and GA to AA (standardized β-coefficient -0.129, 95% confidence interval (CI) -1.82; -0.12; p = 0.025) was observed in the entire cohort. The association was more pronounced among the individuals who were using the device for at least 4 h/night (n = 86; standardized β-coefficient -2.979 (95% CI -6.11; -1.21); p = 0.004)), whereas no significant association was found among the patients who were non-adherent or randomized to no-CPAP. The participants carrying the TNF-α A allele were less responsive to CPAP treatment regarding the decline in circulating TNF-α despite CPAP adherence (standardized β-coefficient -0.212, (95% CI -5.66; -1.01); p = 0.005). Our results suggest that TNF-α (-308G/A) gene polymorphism is associated with changes in circulating TNF-α levels in response to CPAP treatment in adults with CAD and OSA.

Association of TNF-α, IFN-γ, IL-6, and IL-10 with different clinical manifestations of hepatitis B infection

Cytokines have a crucial part in the pathogenesis, persistence of infection, and prognosis of hepatitis B virus (HBV) infection as HBV does not cause direct liver destruction; rather, disease-related complications and prognosis are more associated with immune system action, specifically cytokines such as TNF-α, IFN-γ, IL-6, IL-10, and other cytokines. This study sought to link TNF-, IFN-, IL-6, and IL-10 to various clinical manifestations of HBV infection. Ninety sera were taken from HBV-infected patients, 30 (33.3%) of whom had liver cirrhosis, 30 (33.3%) were HBV carriers, 19 (21.2%) were acute HBV patients, and 11 (12.2%) were recently HBV infected. ELISA was used to determine the serum levels of TNF-α, IFN-γ, IL-6, and IL-10. HBV-infected patients with liver cirrhosis had considerably higher mean serum levels of IFN-γ (P=0.005) and IL-10 (P=0.003), but TNF-α and IL-6 were significantly higher in recent HBV-infected patients (P values 0.034 and 0.004, respectively). There were substantial changes in mean serum levels of TNF-α, IFN-γ, IL-6, and IL-10 at different phases of HBV infection, implying a role for cytokines in HBV etiology, chronicity, and consequences.

Distribution of TNF-α -308 G/A polymorphism among pediatric patients with pneumonia in Ulaanbaatar

Genetic studies indicate to the importance of individual genetic diversity on predictor of mortality. Furthermore, Single Nucleotide Polymorphisms can be used to identify disease-causing genes in humans and they can be either neutral or deleterious. Human Tumor necrosis factor-α is a well-known inflammation factor that is closely associated with sepsis and severe sepsis. Our objective was to evaluate the association of TNF-α -308 G/A promoter polymorphism with dependency to severity of pneumonia. Respiratory diseases, especially pneumonia, is the major cause of mortality and morbidity in Ulaanbaatar, Mongolia and the leading causes of pediatric hospitalization. We collected blood samples from 101 pediatric patients of the age group between "new born" and "school aged", who were treated and diagnosed with pneumonia in February 2019 and 2020, the pneumonia season in the country. Genomic DNA was extracted and performed by PCR-RFLP method to detect the presence of SNPs. The studies showed that the TNF-α -308 G/A polymorphism among pediatric patients, genotype G;G was 73.27%, genotype A;G was 22.77%, and genotype A;A was 3.96%. Our study demonstrated disassociation of TNF-α -308 G/A polymorphism with pneumonia severity in population.

Association of TNF-α (-308G/A) Gene Polymorphism with Circulating TNF-α Levels and Excessive Daytime Sleepiness in Adults with Coronary Artery Disease and Concomitant Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which inflammatory activity has a crucial role. The manifestation of OSA varies significantly between individuals in clinical cohorts; not all adults with OSA demonstrate the same set of symptoms; i.e., excessive daytime sleepiness (EDS) and/or increased levels of inflammatory biomarkers. The further exploration of the molecular basis of these differences is therefore essential for a better understanding of the OSA phenotypes in cardiac patients. In this current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we aimed to address the association of tumor necrosis factor alpha (TNF-α)-308G/A gene polymorphism with circulating TNF-α levels and EDS among 326 participants. CAD patients with OSA (apnea–hypopnea-index (AHI) ≥ 15 events/h; n = 256) were categorized as having EDS (n = 100) or no-EDS (n = 156) based on the Epworth Sleepiness Scale score with a cut-off of 10. CAD patients with no-OSA (AHI < 5 events/h; n = 70) were included as a control group. The results demonstrated no significant differences regarding the distribution of the TNF-α alleles and genotypes between CAD patients with vs. without OSA. In a multivariate analysis, the oxygen desaturation index and TNF-α genotypes from GG to GA and GA to AA as well as the TNF-α-308A allele carriage were significantly associated with the circulating TNF-α levels. Moreover, the TNF-α-308A allele was associated with a decreased risk for EDS (odds ratio 0.64, 95% confidence interval 0.41–0.99; p = 0.043) independent of age, sex, obesity, OSA severity and the circulating TNF-α levels. We conclude that the TNF-α-308A allele appears to modulate circulatory TNF-α levels and mitigate EDS in adults with CAD and concomitant OSA.

The association of TNFα -238 G/A gene polymorphism with alopecia areata

Background/Aim: Alopecia areata (AA), which is characterized by hair loss, is an inflammatory autoimmune disease. Tumor necrosis factor-alpha (TNFα) is a potent proinflammatory cytokine that has a highly significant role in inflammatory and immune responses. The aim of this study is to evaluate whether there is a relationship between TNFα -238 G/A gene polymorphism and AA in the Turkish population. Methods: In this case-control study, the frequency of TNFα-238 G/A gene polymorphism and its relationship with some clinical parameters of AA patients were investigated. Seventy-eight AA patients and 78 healthy individuals were included in our study. TNFα -238 G/A polymorphism was evaluated by the PCR-RFLP method. Results: The distribution of TNFα -238 G/A genotypes was significantly different between patients and control subjects (P

The Association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer's Disease.

Sporadic Alzheimer's Disease (AD) is assumed to be associated with different biological/genetic vulnerability, as well as with neuroinflammation, mediated by cytokines. The present study evaluated the role of cytokines in AD. The aim was to determine the possible association of TNF-α (rs1800629), IL1-α (rs1800587) and IL-10 (rs1800896) polymorphisms with AD, and to assess serum TNF-α, IL-1α and IL-10 concentrations in patients with AD and in subjects with mild cognitive impairment (MCI). The study included 645 Caucasian participants: 395 subjects with AD and 250 subjects with MCI. Genotyping was performed using real-time PCR in all 645 subjects, while serum concentrations of TNF-α, IL-1α and IL-10 and were determined using ELISA in 174 subjects. The frequency of the TNF-α rs1800629, IL1-α rs1800587 or IL-10 rs1800896 genotypes did not differ significantly between patients with AD and MCI. Serum concentration of IL-1α and IL-10 were significantly decreased, while the concentration of TNF-α was significantly higher in patients with AD than in MCI subjects. TNF-α, IL1-α or IL-10 concentrations were similar in subjects with AD or MCI subdivided into carriers of the corresponding TNF-α rs1800629, IL1-α rs1800587 or IL-10 rs1800896 genotypes. Similar distribution of the IL1-α rs1800587, TNF-α rs1800629 or IL-10 rs1800896 genotypes in subjects with AD and MCI failed to confirm that these specific risk genotypes are associated with vulnerability to develop AD. Alteration in IL-1α, IL-10 and TNF-α concentrations in patients with AD partially confirmed the association with the neuroinflammatory response in AD.

Association of Cigarette Smoking With Cerebrospinal Fluid Biomarkers of Neurodegeneration, Neuroinflammation, and Oxidation

Cigarette smoking has been associated with risk of neurodegenerative disorders, such as Alzheimer disease. The association between smoking and biomarkers of changes in human cerebrospinal fluid (CSF) is not fully understood. To investigate the association of cigarette smoking with CSF biomarkers of neurodegeneration, neuroinflammation, oxidation, and neuroprotection. In this case-control study of 191 adult men in China, biomarkers in the CSF of participants with and without significant cigarette exposure were examined. Participants who did not smoke and had no history of substance use disorder or dependence were assigned to the nonsmoking group. The active smoking group included participants who consumed at least 10 cigarettes per day for 1 year. Five-milliliter samples of CSF were obtained from routine lumbar puncture conducted before anterior cruciate ligament reconstruction surgery. Data collection took place from September 2014 to January 2016, and analysis took place from January to February 2016. Cigarette smoking. CSF levels of β-amyloid 42 (Aβ42), which has diagnostic specificity for Alzheimer disease, tumor necrosis factor alpha (TNFα), brain-derived neurotrophic factor (BDNF), total superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured. Sociodemographic data and history of smoking were obtained. Of 191 participants, 87 (45.5%) were included in the active smoking group and 104 (54.4%) in the nonsmoking group. Compared with the active smoking group, the nonsmoking group was younger (mean [SD] age, 34.4 [10.5] years vs 29.6 [9.5] years; P = .01), had more education (mean [SD] duration of education, 11.9 [3.1] years vs 13.2 [2.6] years; P = .001), and had lower body mass index (mean [SD], 25.9 [3.6] vs 24.9 [4.0]; P = .005). Comparing the nonsmoking group with the smoking group, mean (SD) CSF levels of Aβ42 (38.0 [25.9] pg/mL vs 52.8 [16.5] pg/mL; P < .001) and TNFα (23.0 [2.5] pg/mL vs 28.0 [2.0] pg/mL; P < .001) were significantly lower, while BDNF (23.1 [3.9] pg/mL vs 13.8 [2.7] pg/mL; P < .001), total SOD (15.7 [2.6] U/L vs 13.9 [2.4] U/L; P < .001), total NOS (28.3 [7.2] U/L vs 14.7 [5.6] U/L; P < .001), inducible NOS (16.0 [5.4] U/L vs 10.3 [2.7] U/L; P < .001), and constitutive NOS (12.4 [6.9] U/mL vs 4.4 [3.9] U/mL) were higher. In addition, in participants in the smoking group who were aged 40 years or older, total SOD levels were negatively correlated with Aβ42 levels (r = -0.57; P = .02). In those who smoked at least 20 cigarettes per day, TNFα levels were positively correlated with Aβ42 levels (r = 0.51; P = .006). The association of TNFα with Aβ42 production was stronger than that of total SOD with Aβ42 production (z = -4.38; P < .001). This case-control study found that cigarette smoking was associated with at-risk biomarkers for Alzheimer disease, as indicated by higher Aβ42 levels, excessive oxidative stress, neuroinflammation, and impaired neuroprotection found in the CSF of participants in the active smoking group.

Associations of TNF-α -238G/A, TNF-α -308G/A, and IL-6 -174G/C polymorphisms with the risk of asthma: Evidence from a meta-analysis.

Previously, many genetic epidemiological studies have investigated associations between Th1-related cytokine polymorphisms and the risk of asthma, with inconsistent results. Accordingly, we carried out a meta-analysis to more precisely estimate associations between Th1-related cytokine polymorphisms and the risk of asthma. Systematic literature searching of Medline, Embase, Wanfang, VIP, and CNKI was conducted by the authors to identify eligible publications, and 69 genetic epidemiological studies were finally found to be eligible for quantitative analyses. We found that genotypic frequencies of TNF-α -238G/A (dominant comparison: odds ratio [OR] = 0.47, P = .006; overdominant comparison: OR = 1.87, P = .03; allele comparison: OR = 0.50, P = .004), TNF-α -308G/A (dominant comparison: OR = 0.76, P = .001; overdominant comparison: OR = 1.29, P = .002; allele comparison: OR = 0.81, P = .0009) and IL-6 -174G/C (dominant comparison: OR = 0.55, P = .0008) polymorphisms among patients with asthma and control subjects were significantly different. However, we did not detect such a genotypic distribution difference for the IL-1B-511C/T polymorphism. The present meta-analysis shows that TNF-α -238G/A, TNF-α -308G/A, and IL-6 -174G/C polymorphisms may influence the risk of asthma.

Abstract P023: Relationship Between TNF-α And SBP In The Baseline Cohort Of The Dietary Approaches To Stop Hypertension (DASH)-Sodium Trial

Hypertension (HTN) is a leading global noncommunicable cause of mortality and dietary salt is the most common modifiable risk factor for HTN. Evidence suggests that tumor necrosis factor alpha (TNF-α) modulates mechanisms that may contribute to salt-sensitive hypertension (SSHT). We conducted a secondary analysis of the baseline cohort of the DASH-Sodium trial, to explore the relationship between TNF-α and systolic blood pressure (SBP) in subjects categorized by race, sex, and baseline blood pressure. Urinary TNF-α levels adjusted for creatinine (pg/mg) were measured in (91%) (374 of 412) subjects ingesting high salt (150 mmol) and control diet for 2 weeks prior to randomization. Descriptive analyses were used to determine the sample prevalence of demographic, laboratory, and outcome variables, and bivariate analyses were used to check for highly correlated variables. Robust multiple linear regression was used to evaluate the association of TNF-α and SBP with and without covariates, p &lt; 0.05. SBP, urinary sodium and potassium adjusted for creatinine, and 24-hour urine volume were positively associated with TNF-α, whereas African American, male, and increasing waist circumference exhibited negative associations with TNF-α, p &lt; 0.05. Predicted TNF-α increased from 22.7 (19.3,26.8) to 33.2 (26.9,41.0) pg/mg with increasing SBP (100 to 180 mm Hg). TNF-α was 25.4 (23.7, 27.1) pg/mg for AA vs. 28.9 (27.2, 30.8) pg/mg for non-AA, and 24.2 (22.6, 25.9) for males vs. (27.3, 30.7) pg/mg for females, respectively. TNF-α increased from 22.3 (20.3, 24.5) to 46.8 (36.1, 60.7) pg/mg as urinary potassium increased from 10 to 100 mg/g, and from 22.7 (20.3, 25.5) to 33.1 (29.0, 37.8) pg/mg as urinary sodium increased from 10 to 250 mg/g. There was a statistically significant interaction between urinary sodium and potassium: TNFα increased to a greater extent with increasing urinary potassium at a lower level of urinary sodium (-1 SD),16.7 (14.0, 20.2) to 38.1 (31.3, 47.3) pg/mg compared to that at higher urinary sodium levels (+1SD), 24.4 (21.0, 28.4) to 35.2 (30.9, 40.1) pg/mg. These results suggest that TNF-α may regulate ion transport mechanisms that contribute to differences in potassium handling and changes in sodium and potassium excretion observed in SSHT.

Role of TNF-α and FGF-2 in the Fracture Healing Disorder of Type 2 Diabetes Model Induced by High Fat Diet Followed by Streptozotocin.

PurposeTo investigate the effect of TNF-α and FGF-2 in the fracture healing disorder of type 2 diabetes.Design/Methodology/ApproachRat diabetes-bone traction model was established to investigate the effect of type 2 diabetes on the fracture healing and the association of TNF-α and FGF-2 with the process. Serological examination was performed to detect the related diabetes indexes. The proliferation activity of the cells was detected by MTT assay. The expressions of FGF-2 and TNF-α of osteoblasts in high glucose culture environment were detected by histochemistry and Western blotting.FindingsSerological examination showed that in rats fed with high fat and sugar diet for 8 weeks, the serum total cholesterol (TC), triglyceride (TG), fasting insulin (FINs) significantly increased, but fasting blood glucose (FBG) had no significant change. Two weeks after intraperitoneal injection of STZ, rat serum TG, TC, and FBG increased significantly, while FINs did not change obviously. Two weeks after traction osteogenesis, X-ray examination and HE staining showed that the area of osteotylus in the diabetes group was significantly smaller than that in the control group. The number of PCNA positive cells in the osteotylus of diabetes group was significantly decreased. In the osteotylus of diabetes group, the expression of TNF-α was significantly increased and the expression of FGF-2 was significantly decreased. MTT assay showed that the proliferation activity of MC3T3-E1 cells in high glucose culture medium groups was significantly decreased at 24th hour of the culture, compared with the normal culture medium group. qPCR results showed that the expression of FGF-2 was significantly decreased while the expression of TNF-α was significantly increased in high glucose culture medium groups.Originality/ValueIt was concluded that type 2 diabetes mellitus affected the fracture healing by causing osteoblast proliferation disorder. TNF-α and FGF-2 were important related factors for the process.

Transcriptional elucidation of tumor necrosis factor-α-mediated nuclear factor-κB1 activation in breast cancer cohort of Pakistan.

Initiation, promotion, progression, and metastasis of mammary tumors are mediated by dysregulation of multiple genes involved in various signaling pathways. Expressional variation of these molecules significantly influences cancer cell proliferation in breast cancer. In the current study, tumor necrosis factor-alpha (TNF-α) and its downstream effector nuclear factor kappa-B1 (NF-κB1) mean transcript levels were explored and associated with molecular subtypes in breast cancer cohort of Pakistan. Freshly excised tumors (n = 150) along with background tissues were collected for RNA isolation and cDNA synthesis. Quantitative polymerase chain reaction was carried out for quantification of TNF-α, NF-κB1, and β-actin gene transcripts along with estrogen receptor, progesterone receptor, HER2, and Ki-67, followed by statistical analysis. For TNF-α and NF-κB1, 95% and 77% of the cohort was found to be positive, respectively. Both of these molecules were found to be significantly upregulated in tumors when compared against their respective controls (P < 0.0001). Association of TNF-α and NF-κB1 with late clinical stages, poorly differentiated tumors, increased tumor size, nodal involvement, and metastasis was observed to be statistically significant (P < 0.05). Strong positive correlation was established between TNF-α and NF-κB1(r = 0.465, P< 0.05). Moreover, mean transcript levels of TNF-α and NF-κB1 were significantly elevated in Luminal A and Luminal B subtypes of breast cancer patients, respectively. Strong positive correlation between TNF-α and NF-κB1 proposed the putative role of these molecules as prognostic biomarkers in breast cancer.

Association of TNF-&#945; -308G&gt;A Polymorphism with Susceptibility to Cervical Cancer and Breast Cancer - a Systematic Review and Meta-analysis.

To date, several studies have been carried out on the association of TNF-&#945; -308G&gt;A with the risk of cervical cancer (CC) and breast cancer (BC). However, their conclusions were not consistent. Thus, we performed a comprehensive meta-analysis to evaluate the association more precisely from all eligible case-control studies. We searched the PubMed, Google Scholar and Cochrane Library databases systematically to identify relevant studies up to 1 February 2019. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a fixed-or random-effects model. A total of 40 case-control studies including 20 studies with 4,780 cases and 4,620 controls on CC and 20 studies with 12,390 cases and 14,910 controls on BC were selected in this meta-analysis. The pooled results showed that the TNF-&#945; -308G&gt;A polymorphism was significantly associated with an increased risk of CC (A vs. G: OR 1.277; 95% CI 1.104-1.477; P = 0.001; AA vs. GG: OR 1.333; 95% CI 1.062-1.674; P = 0.013; AG vs. GG: OR 1.307; 95% CI 1.064-1.605; P = 0.011; and AA + AG vs. GG: OR 1.324; 95% CI 1.104-1.587; P = 0.002) and BC (AA vs. AG + GG: OR 0.094; 95% CI 0.058-0.152; P 0.001). In the stratified analyses by ethnicity, the TNF-&#945; -308G&gt;A polymorphism was significantly associated with the risk of CC (in Caucasians and Africans) and BC (Caucasians and Asians). Our findings showed that TNF-&#945; -308G&gt;A polymorphism may be a risk factor for cervical cancer and breast cancer overall and by ethnicity.

Tumor Necrosis Factor-α -308G/A Genetic Polymorphism and the Susceptibility of Posttraumatic Sepsis

Summary of background data The association between tumor necrosis factor α (TNFα) -308G/A polymorphism and susceptibility to posttraumatic sepsis has been studied extensively. But the results have not remained very clear. Purpose We carried out this meta-analysis to explore the influence of TNF on susceptibility to posttraumatic sepsis. Methods Relevant studies were identified from PubMed, Web of Science, Embase, and China National Knowledge Internet without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Results Seven case-control studies were included in the meta-analyses on the association of TNFα -308 G/A genetic polymorphism and risk of posttraumatic sepsis. TNFα -308 G/A genetic polymorphism was significantly associated with susceptibility to posttraumatic sepsis in the dominant model [odds ratio (OR), 2.17; 95% confidence interval (95% CI), 1.19–3.95; P = 0.011] and allelic model (OR, 1.72; 95% CI, 1.23–2.39; P = 0.001), but not in the heterozygous model (OR, 1.38; 95% CI, 0.58–3.39; P = 0.489). There was no significant publication bias for these 3 models. However, marked heterogeneity existed in the dominant model (I2 = 68.9%, P = 0.004) and the heterozygous model (I2 = 68.9%, P = 0.022). Conclusions TNF -308 G/A genetic polymorphism may have an influence on susceptibility to posttraumatic sepsis. Further studies with large sample sizes and well-designed studies are needed to confirm these results.

Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in India

Host genetic factors are frequently ascribed to differential malaria outcomes as a by-product of evolutionary adaptation. To this respect, Tumor Necrosis factor alpha (TNF-α), a human cytokine, is known to be associated with malaria through its differential regulation in diverse malaria manifestations. Since diversity in differential malaria outcome is uncommon in every endemic settings, possible association of TNF-α and malaria is not commonly established. In order to check for association between the occurrence of Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene with different malaria manifestations, we have sequenced a 4011 bp region constituting the promoter and the whole gene of human TNF-α in 61 patients [(16 cerebral plus severe (SCM), 21 severe (SM) and 24 uncomplicated (UM)] samples in a highly malaria endemic state (Odisha) of India. Multiple sequence alignment revealed presence of six SNPs (−1031 T > C, −863C > A, −857C > T, −308G > A, −806C > T, +787C > A), out of which the -806C > T and +787C > A are novel in malaria patients in general and the +787C > A was detected for the first time in humans. Although alleles due to six different SNPs segregate differentially in the three groups of malaria (SCM, SM and UM) in the present study, interestingly, for the −1031 T > C position, the frequency of individuals possessing the homozygous rare allele was higher in the SCM group with a higher number of heterozygotes in the UM group. The Tajima's D values considering all the SNPs in a defined group were positive and statistically insignificant conforming no evolutionary constraint. However, statistically significant deviation from expectation under Hardy-Weinberg equilibrium for -1031 T > C SNP in the UM group points towards the probable role of natural selection providing some kind of protection to malaria in Odisha, India.

A trial sequential meta-analysis of TNF-α -308G>A (rs800629) gene polymorphism and susceptibility to colorectal cancer.

Purpose: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-α –308 G>A (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-α –308 G>A gene polymorphism with CRC risk.Methods: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association.Results: The pooled analysis indicated no risk associated with TNF-α –308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863–1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688–2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843–1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849–1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686–2.033). Subgroup analysis revealed that TNF-α –308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias.Conclusions: No association of TNF-α –308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α –308 G>A SNP in the etiology of CRC and to endorse the present findings.

TNF-α -308G/A gene polymorphism in bullous pemphigoid and alopecia areata.

TNF-α -308G/A polymorphism has been investigated in few studies for an association with susceptibility to bullous pemphigoid (BP) and alopecia areata (AA). Yet, these findings had so far not been independently replicated, and no data on a possible association of TNFα -308G/A polymorphism with these diseases in Iranian population were available. In the present study, a possible effect of TNF-α -308G/A variation on susceptibility to BP or AA disease was evaluated. Genomic DNA was extracted from the blood of the patients with BP and AA as well as control subjects which genotyped for the TNF-α -308 G/A polymorphism. TNF-α gene expression levels were analyzed by real-time RT-PCR. No association was observed between the TNF-α -308 G/A variation and susceptibility to BP or AA diseases in our Iranian cohort. In contrast to AA patients, expression of TNF-α gene was significantly higher in BP patients compared to control group. TNF-α gene was found to be similarly expressed in mutant and wild-type genotypes. TNF-α -308G/A polymorphism is not associated with the risk to develop of BP and AA in our Iranian cohort. Furthermore, this polymorphism is contributed to altering the levels of gene expression in BP disease.