Association of TNF-?-308G/A, -238G/A, -863C/A, -1031T/C, -857C/T polymorphisms with periodontitis susceptibility: Evidence from a meta-analysis of 52 studies.
ABSTRACT: The association between tumor necrosis factor-alpha (TNF-?-308G/A, -238G/A, -863C/A, -1031T/C, and -857C/T) polymorphism and either chronic (CP) or aggressive (AgP) periodontitis susceptibility was conflicting. This meta-analysis aimed to quantitatively estimate the association.A total of 52 studies involving 5519 patients and 7260 controls were identified through a search of multiple electronic databases. Odds ratios (ORs) and their 95% confidence intervals using allele, homozygous, heterozygous, dominant, and recessive genetic models were computed to assess the strength of the association.The TNF-?-308G/A polymorphism was significantly associated with decreased risks of CP (GG vs AA: OR?=?0.353, P?
Project description:BACKGROUND: Epidemiological studies have evaluated the association between tumor necrosis factor ? (TNF-?) single nucleotide polymorphisms (SNPs) and duodenal ulcer (DU), but the results remain inconclusive. The aim of this study was to perform a meta-analysis to investigate a more authentic association between TNF-? SNPs and DU. METHODS: We performed the meta-analysis by searching PubMed, Embase, and Web of Science databases from the first available year to Sep. 5, 2012. Additionally, checking reference lists from identified articles, reviews, and the abstracts presented at related scientific societies meetings were also performed. All case-control studies investigating the association between TNF-? SNPs and DU risk were included. The association was assessed by odds ratio (OR) with 95% confidence interval (CI). Publication bias was analyzed by Begg's funnel plot and Egger's regression test. RESULTS: A total of sixteen studies reporting TNF-? -308G/A, -1031T/C, -863C/A, -857C/T, and -238G/A polymorphism were included in our final meta-analysis. There was no statistically significant association between -308G/A polymorphism and DU in the overall study population, as well as subgroup analyses by ethnicity, study design, and H. pylori status. As for -1031T/C, -863C/A, -857C/T, and -238G/A, results of our meta-analyses showed no statistical evidence of significant association. Power calculation on the combined sample size showed that the statistical powers were all lower than 80% for all the meta-analyses. CONCLUSIONS: The data suggests that there is no statistical evidence of significant association between the studied TNF-? SNPs and DU. However, this conclusion should be interpreted with caution as low statistical powers were revealed by power calculations. In future, larger sample-size studies with homogeneous DU patients and well-matched controls are required.
Project description:A number of studies had reported the association between tumor necrosis factor-alpha (TNF-?) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship.We systematically searched electronic databases (PubMed, the Web of Science, EMBASE, Medline, Chinese National Knowledge Infrastructure, WanFang and ChongQing VIP Database) for relevant studies published up to February 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for assessing the association. The present meta-analysis was performed using STATA 12.0 software.In total, 45 articles with 17,375 cases and 15,375 controls involved were included. Pooled ORs revealed a significant association between TNF-? -308G/A gene polymorphism and IHD (A vs. G: OR?=?1.22, 95% CI?=?1.10-1.35; (AA?+?GA) vs. GG: OR?=?1.18, 95% CI?=?1.03-1.36; (AA vs. (GA+GG): OR?=?1.37, 95% CI?=?1.08-1.75)), indicating that the TNF-? -308A allele might be an important risk factor for IHD. No association between other TNF-? gene polymorphisms and susceptibility to IHD were observed. No publication bias were found. Sensitivity analyses indicated that our results were stable.The present study indicated a possible association between the TNF-? -308G/A gene polymorphism and IHD risk. However, evidence was limited to confirm the role of TNF-? -238G/A, -857C/T, -863C/A, -1031T/C and other TNF-? gene polymorphisms in the risk of IHD.
Project description:<h4>Background</h4>Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-?. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection.<h4>Methods</h4>Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI).<h4>Results</h4>A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43-0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43-0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44-0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16-1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14-1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup.<h4>Conclusion</h4>Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results.
Project description:Although the etiology of Behçet's Disease (BD; MIM 109650) remains to be clearly elucidated, levels of tumor necrosis factor alpha (TNF-alpha) have been reported to be significantly elevated in BD patients, and TNF-alpha blockers have been demonstrated to exhibit some degree of therapeutic efficacy for a certain subset of BD sufferers. In this study, we have conducted an analysis of the TNFA haplotypes in the promoter response element that affect the binding affinity of specific transcription factors, in order to characterize their association with the clinical features of BD. Six polymorphisms in the promoter region of TNFA were genotyped in 254 BD patients and 344 control subjects, via the PCR-RFLP technique. TNFA -1031*C, -863*A and -308*G alleles were associated with an increased risk of BD (p=0.030, OR=1.4; p=0.008, OR=1.5; p=0.010, OR=1.8, respectively). The sole TNFA haplotype -1031C-863A-857C-376G-308G-238G, was associated with a 1.6 fold increase in the risk of BD, whereas the TNFA haplotype -1031T-863C-857C-376G-308A-238G was associated with a 0.6 decreased risk of BD. The TNFA -1031*C, -863*A, -857*C and -308*G alleles were significantly associated with BD. The findings of this study, collectively, indicate that TNFA haplotypes in the promoter response elements may exert significant influence on susceptibility to BD.
Project description:Health of the metal industrial workers should be a noteworthy issue due to the hazard ofchronic exposure to metals or toxic elements. The interactions among multiple elements aresophisticated and may differ from person to person. Tumor necrosis factor-? (TNF-?) genepolymorphisms were supposed to be involved with the interactions because TNF-? plays animportant role in inflammation, a mechanism by which toxic elements cause threats to humanhealth. This research aimed to analyze the influence of TNF-? gene polymorphisms and multielementson serum TNF-? level. Blood multi-elements concentrations (lead, cadmium, arsenic,selenium, cobalt, copper, and zinc), serum TNF-? level, and TNF-? single nucleotidepolymorphisms (SNPs), including -238G > A (rs361525), -308G > A (rs1800629), -857C > T(rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964), were measured in 462 metalindustrial workers. We applied mixed-effect models to analyze the interactions among multielementsand TNF-? SNPs. Blood concentration of all elements were positively associated withserum TNF-? level, and the effects may be modified by TNF-? gene polymorphisms. Our studyrevealed that TNF-? -308A/A and -1031C/C may be susceptible genotypes, and thus we suggestthat those workers should take preventive measures against metal toxicity.
Project description:This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-?) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-? gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-? -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-? -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-? -238G>A, while TNF-? -308G>A is in African population.
Project description:BACKGROUND:Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-? (TNF-?) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF-? promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes. METHODS:A total of 231 patients with CHB constituted the study group and 100 healthy volunteers-the local control group. TNF-? -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped using MALDI-TOF mass spectrometry. RESULTS:TNF-? -1031C and -863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-? -1031C and -863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A -857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF-? variants and liver fibrosis were found. CONCLUSION:This study indicates that TNF-? -863A and -1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.
Project description:Background: Periodontitis is a very common inflammatory oral disease. Tumor necrosis factor-? (TNF-?) is a cytokine that has been involved with the gingival tissue destruction and remodeling occurrence. We investigated the association of single nucleotide polymorphisms (SNPs) in TNF-? gene promoter region with the susceptibility of aggressive and chronic periodontitis in the eastern Indian population.Methods: A total of 397 DNA samples from venous blood were isolated. 40 individuals were aggressive periodontitis patients, 157 were identified chronic periodontitis patients, and the remaining 200 were healthy individuals. Five SNPs of TNF-? at promoter region (rs361525, rs1800629, rs1799724, rs1800630, and rs1799964) were genotyped by PCR-sequencing in periodontitis patients and control subjects.Results: rs1800629 (-308G/A) polymorphism was more frequent in both aggressive and chronic periodontitis patients compared with the control population, though the allele frequency was different only in aggressive periodontitis patients. On the other hand, both the genotypic and allelic variation of rs361525 (-238G/A) polymorphism were found significantly less frequently in aggressive and chronic periodontitis than in controls. The other polymorphisms like rs1799724 (-857C/T) and rs1799964 (-1031T/C) were significantly different between chronic periodontitis patients and control subjects.Conclusion: The findings suggest that the rs1800629 (-308G/A) polymorphism of TNF-? gene is associated with both aggressive and chronic periodontitis while rs1799724 (-857C/T) and rs1799964 (-1031T/C) polymorphisms of TNF-? gene is associated only with the increased susceptibility to chronic periodontitis.
Project description:Background:Tumor necrosis factor-alpha (TNF-?) is an important cytokine in acute inflammatory response to infective factors. Based on investigation in different populations, it is thought that this response increases in patients with endometriosis due to the presence of cytokines such as TNF-?. This study aimed to examine the association of four TNF-? polymorphisms, namely -238G/A, -308G/A, -857C/T and -863C/A, with susceptibility to endometriosis in an Iranian population. Materials and Methods:We recruited 150 women with endometriosis and 150 women without endometriosis in this case-control study and collected 4 ml of blood from all subjects. After DNA extraction, the polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results:The allele frequency of TNF-? -863C/A in the case and control groups showed a significant difference [odds ratios (OR)=0.64, 95% confidence interval (CI)=0.41-0.99, P=0.047] but the result is not significant when Adjusting for multiple testing (P=0.188). No significant difference in the allele frequencies of -238G/A (OR=1.07, 95% CI=0.51-2.25, P=0.862), -308G/A (OR=0.79, 95% CI=0.43-1.45, P=0.438) and -857C/T (OR=1.03, 95% CI=0.66- 1.61, P=0.887) was observed. We adjusted all four polymorphism genotypes by age and body mass index (BMI), however, no significant difference was detected. There was an association between the case and control and BMI when adjusting by age (OR=1.082, 95% CI=1.009-1.162, P=0.028). Conclusion:For the first time the association of the four polymorphisms in the promoter region of the TNF-? gene with endometriosis has been conducted in women of Iranian origin. The present research reveals the -863 A allele may play a role in incidence of endometriosis among Iranian women. Development of endometriosis among those people with -863 A allele seems low. According to the results, the current study indicates that there might be a correlation between BMI and progression of endometriosis.
Project description:Purpose:To explore the cause of functional changes of tumor necrosis factor alpha (TNF-?) in development of gastric cancer through the structural changes of each site in TNF-? before and after mutation. Methods:Three typical mutant sites (TNF-?-308G/A, 857C/T and 863C/A of TNF-?) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-? before and after mutation, besides, the structural changes were also analyzed. Results:Mutation of TNF-?-308G/A led to the production of multiple helical structures and that of 863C/A caused the production of one helical structure in its adjacent region. Mutation of 857C/T, however, did not cause the change in the basic structure of TNF-?. Conclusions:Structural changes of TNF-? may have a significant effect on development of gastric cancer.