TNF-α Gene Polymorphisms Research Articles

Genetic predisposition of TNFα gene polymorphism in South-Indian Migraineurs and meta-analysis.

Migraine (Mg) is a multifaceted neurovascular disorder caused by genetic and several environmental etiologies. We have implemented a case-control study of TNFα gene polymorphism in 212 Mg patients and 218 healthy controls utilizing the ARMS-PCR technique, followed by Sanger sequencing. Besides, we have conducted a meta-analysis of different genetic models (five genetic models) to combine and summarize the available data from 11 studies (including this present research). The strength of genetic associations in the meta-analysis used to assess by the pooled odds ratio (OR) and 95% confidence intervals (CI). The results of this case-control study discovered a significant relationship with Mg in recessive and homozygous genotype with OR = 2.35 (95% CI [0.96-5.74]), p-value = 0.045. Also, the outcomes of meta-analysis suggested an irrelevant relationship between TNFα gene (rs1800629) polymorphism and Mg susceptibility in the five genetic models. However, subgrouping based on ethnic background showed a significant association in the allelic genetic model with OR = 1.53 (95% CI [1.02-2.31]), p = 0.040 respectively. The meta-analysis results of TNFα gene polymorphism may represent a risk factor for Mg among Asians. In the future, large scale, multicentric case-control study by classification of patients with Mg with or without aura can be performed worldwide to identify the potential genetic risk factors leading to Mg pathogenesis.

Meta-analysis on association between TNF-α and CCR5Δ32 gene polymorphisms and influenza A(H1N1)pdm09

Objective: To investigate the associations between TNF-α and CCR5Δ32 gene polymorphisms and influenza A(H1N1)pdm09. Methods: Studies in PubMed, Cochrane Library, OVID, EBSCO, Web of Science published before February 7, 2019 were retrieved comprehensively. Observational studies related to TNF-alpha and CCR5 gene polymorphisms and influenza A(H1N1) pdm09 were collected. A strict quality evaluation was carried out according to NOS scale. Meta-analysis was performed using software Revman 5.0 and Stata 11.0. Results: After screening, a total of 8 studies were included in this Meta-analysis. The results showed that TNF-α gene polymorphism rs361525 might be associated with the risk of influenza A(H1N1)pdm09 virus infection (A vs. G: OR=2.25, 95%CI: 1.09-4.65, P=0.03; AA vs. GG: OR=4.34, 95%CI: 1.65-11.41, P=0.003; AA vs. AG+GG: OR=4.38, 95%CI: 1.67-11.48, P=0.003), similar trend also found in rs1800750 (AA+AG vs. GG: OR=2.42, 95%CI: 1.24-4.71, P=0.01). The results of subgroup analysis indicated that A allele and AA+AG genotypes of rs361525 were risk factors for influenza A(H1N1) pdm09 virus infection in Caucasians. AA genotype was a risk factor for influenza A(H1N1) pdm09 virus infection in Mexican (P<0.05). There was no significant difference in the genetic polymorphism of CCR5 and the severity of influenza A (H1N1) pdm09 virus indection (P>0.05). Conclusion: People with allele A or genotype AA at rs361525, genotype AA+AG at rs1800750 of TNF-α gene might be more susceptible to influenza A(H1N1) pdm09.

Tumor Necrosis Factor-alpha (TNF-α) −238 G/A Polymorphism Is Associated with the Treatment Resistance and Attempted Suicide in Schizophrenia

ABSTRACT Abnormality of the immune system may play an important role in the pathogenesis of schizophrenia (SCZ). We aim to investigate the relationship between clinical features of SCZ and tumor necrosis factor-alpha (TNF-α) −238 G/A, −308 G/A polymorphisms in SCZ patients by comparing genotype distributions of TNF-α gene polymorphisms between patients and healthy controls. A sample of 113 patients with SCZ and 104 healthy volunteers was included in the study. SCID-I was used to confirming the diagnosis according to DSM-IV-TR criteria. We evaluated the patients with some scales and data forms in terms of clinical features, symptom severity, level of insight, suicidal behavior, and treatment response. PCR-RFLP was used to determine TNF-α gene polymorphisms from DNA material. The distributions of TNF-α − 238 G/A and TNF-α − 308 G/A polymorphisms of the patients diagnosed with SCZ were not significantly different from the control group. There was a significant difference in the TNF-α − 238 G/A genotype distributions between treatment-resistant and treatment-responsive SCZ patients. Again, the distributions of TNF-α − 238 G/A genotype of attempted suicide patients in SCZ were significantly different from the non-attempted suicide of SCZ patients. Whereas TNF-α − 238 G/A and −308 G/A polymorphisms were not associated with SCZ, TNF-α − 238 G/A polymorphism may be related to treatment resistance and attempted suicide in SCZ patients in the Turkish population.

Tumor Necrosis Factor Alpha-863 C/A Single Nucleotide Polymorphisms and Nephrotic Syndrome

Introduction: Cytokines act as a mediator of inflammation in childhood nephrotic syndrome. Polymorphisms of cytokines genes may influence susceptibility to nephrotic syndrome (NS), as well as, patients’ steroid responses. Objective: To study the association of tumor necrosis factor-alpha single nucleotide polymorphisms (TNF-α SNP) (-863 C/A) with the development of NS in addition to access to their effects on serum level of TNF and the response to steroid therapy. Patients and Methods: This study included 60 patients (19 female and 41 male) with nephrotic syndrome; their ages ranged from 2 to 18 years. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess the TNF-α gene polymorphism. Results: According to the digestion pattern of RFLP-PCR products of TNF-α-863, this polymorphism had three genotypes, which were CC, CA, and AA, in both NS patients and controls. Also, the current result observed that -863 SNP do not affect the serum level of TNF-α and steroid responsiveness in patients with nephrotic syndrome. Conclusion: This polymorphism did not show any significant association with response to steroid therapy and TNF serum level neither at genotype nor at allele level.

Correlation of TNF-α and IL-10 gene polymorphisms with primary nephrotic syndrome.

The study explored the correlations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) gene polymorphisms with susceptibility and the condition of primary nephrotic syndrome. A total of 200 patients with primary nephrotic syndrome in Qilu hospital were collected as disease group, and 200 healthy people were selected as control group. Genomic deoxyribonucleic acids (DNAs) of nucleated cells in the peripheral blood were extracted to detect the gene polymorphisms of TNF-α (rs1799724 and rs1800629) and IL-10 (rs1800872 and rs141219090). Allele distributions at rs1799724 (P=0.003) and rs1800629 (P=0.011) of TNF-α gene and at rs1800872 (P=0.033) of IL-10 gene in disease group were different from those in control group. In the disease group, allele C frequency at rs1799724 and allele A frequency at rs1800629 of TNF-α gene and allele T frequency at rs1800872 of IL-10 gene were higher. There were differences between rs1799724 (P=0.007) and rs1800629 (P=0.002) of TNF-α gene. In addition, there was a difference in the frequency of the dominant model of TNF-α gene rs1800629 between disease group and control group (P=0.035), and the frequency of dominant model GG+GA was remarkably lower in the disease group. Additionally, TT genotype at rs1799724 of TNF-α gene was obviously related to the plasma TNF-α level (P<0.05), and the plasma TNF-α level was significantly increased in disease group. AA genotype at rs141219090 of IL-10 gene had a notable correlation with the plasma IL-10 level (P<0.05), and the plasma IL-10 level in disease group was markedly raised. Additionally, CT genotype at rs1799724 of TNF-α gene was related to the 24-h urine protein level (P=0.035), GG genotype at rs1800872 of IL-10 gene was associated with the plasma albumin level (P=0.031), and GG genotype at rs141219090 was related to the serum creatinine level (P=0.047). TNF-α and IL-10 gene polymorphisms are predominantly correlated with the susceptibility and the condition of primary nephrotic syndrome.

LTA, LEP, and TNF-a Gene Polymorphisms are Associated with Susceptibility and Overall Survival of Diffuse Large B-Cell lymphoma in an Arab Population: A Case-Control Study.

Objective:In this study, we aimed to explore the relationship between five selected proinflammatory and immune-mediated genes (TNF rs1800629G>A, rs361525G>A, rs1799964T>C, LTA rs1800683G>A, rs909253A>G, TNFAIP8 rs1042541C>T, LEPR rs1327118G>C, and LEP rs2167270G>A) and the risk and overall survival of DLBCL patients within the Jordanian Arab population. Methods:One hundred twenty-five patients (125) diagnosed with DLBCL at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 238 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects and from peripheral blood samples of the controls. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. Results:Our study showed significant differences in the distribution of the studied polymorphisms of DLBCL between the patients and controls for TNF rs1800629G>A, LTA rs909253 G>A and LEP rs2167270 G>A. TNF rs1800629G>A (p = 0.01), in which the G allele harbors a higher risk of DLBCL (GG and GA genotypes when compared with AA genotype) (p = 0.044). The LTA rs909253 A>G polymorphism is associated with a higher risk of DLBCL in the allelic model (p = .004). LEP rs2167270 G>A polymorphism is associated with a decreased risk of DLBCL in the recessive mode models (p = .03). Subjects with the dominant model for TNF-a rs1799964 (TT genotype in comparison with the combined TT/TC genotype) and patients with the homozygous genotype (GG) of rs361525 have better overall survival rates. Conclusion:Our results confirmed the diversity and the heterogeneity of the disease. Although the study has a limitation because of its relatively small size, it clearly emphasizes the significance of ancestry and genetic composition as the determinants of DLBCL risk and behavior.

ALL-232: Genetic Variants of Tumor Necrosis Factor α and Interleukin-10 in Childhood and Adult Acute Lymphoblastic Leukemia

Context Interleukin-(IL)10 and tumor necrosis factor (TNF) a have a significant role in malignancies. Genes encoding these cytokines are linked with different levels of gene transcription. Objective Analyzing IL-10 and TNFα gene polymorphisms and their contribution to ALL prognosis and survival. Design This prospective observational study was conducted from June 2017 until Oct 2019. Setting Oncology Center Mansoura University, Egypt. Patients or other participants We genotyped 64 children and 76 adult ALL patients for IL-10-1082A > G and TNFα-308G > A polymorphisms in the gene promoter region. We used polymerase chain reaction (restriction fragment length polymorphism method) for the molecular analysis. Results Pediatric ALL patients showed TNFα A allele and IL-10 A allele, which were associated with older age (p = 0.04, 0.03), extramedullary disease (p = 0.04, 0.001), and carried Philadelphia chromosome (p = 0.02, 0.001), compared to the G allele, respectively. IL-10-1082AA and TNF 308AA genotypes carried on the Ph-positive chromosome were associated with a longer time to CR and a higher rate of relapse than other genotypes. The IL-10 (GG) genotype was associated with significant improvement of OS compared to IL-10 (GA) and (AA) genotypes (p = 0.026). The adult ALL patients carrying the A allele of TNFα had a higher rate extramedullary disease (p = 0.009) and a higher rate of relapse (p = 0.003). Also, we found increased frequency of the IL-10-A allele with advanced age (p = 0.03), lower Hb level (p = 0.04), increased extramedullary disease (p = 0.001), and Ph chromosome positivity (p = 0.001), which resulted in longer time to CR (p = 0.003) and high relapse rate (p = 0.002). IL-10 (AA) and TNFα (AA) genotype patients were associated with extramedullary disease, carried the Ph-positive chromosomal abnormality, and had a higher rate of relapse than other genotypes among adult ALL patients. Patients with IL-10 (GG) and TNFα (GG) genotypes did not show significant improvement of OS and RFS by Kaplan-Meier curves (p > 0.05) compared to other genotypes. Conclusion IL-10 (AA) and TNFα (AA) were associated with poor prognostic factors in childhood and adulthood ALL. This might modulate the risk, overall survival, and relapse-free survival among ALL patients.

Systematic review and meta-analysis of association of polymorphisms in inflammatory cytokine genes with coronary artery disease.

It has comprehensively beenacknowledged that a genetic contribution, especially in immune inflammatory players, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are critically involved in the pathophysiology of coronary artery disease (CAD). This meta-analysis study aimed to reach a conclusive understanding of the role of genetic polymorphisms, including IL6 gene C572G (rs1800796) and G174C (rs1800795) as well as TNFA gene G238A (rs361525) and G308A (rs1800629) in susceptibility to CAD. Two major databases, namely MEDLINE and Scopus, were searched to find the studies surveying the mentioned polymorphisms and CAD susceptibility up to July 2020. Association comparison between the polymorphisms and CAD susceptibility were assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). This meta-analysis study was conducted on 69 papers (73 population studies), comprising 5062 patients and 8446 controls for IL6 gene rs1800796 (17 studies), 13801 patients and 16215 controls for IL6 gene rs1800795 (38 studies), 1439 patients and 2850 controls for TNFA gene rs361525 (5 studies), and 5051 patients and 3958 controls for TNFA gene rs1800629 (13 studies), according to inclusion and exclusion criteria. There were statistically positive association between all genetic comparisons of IL6 gene rs1800795 polymorphism and the CAD risk. Moreover, the recessive model (CC vs. CG + GG) in IL6 gene rs1800796 polymorphism had marginally significant association with decreased risk of CAD. None of the TNFA gene polymorphisms were associated with CAD risk. The meta-analysis revealed the positive association of IL6 gene rs1800795 polymorphism in susceptibility to CAD.

Associations of the -238(G/A) and -308(G/A) TNF-α Promoter Polymorphisms and TNF-α Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to Helicobacter pylori Infection in a Moroccan Population.

Objective: Helicobacter pylori (H. pylori) induces the production of tumor necrosis factor-alpha (TNF-α), which is closely related to a gastric epithelial injury. TNF-α gene polymorphism and TNF-α serum levels are associated with various malignant conditions. Identification of the ideal marker for gastric cancer (GC) is still the leading aim of several trials. Physio-pathological considerations of GC led us to investigate the association of two TNF-α promoter polymorphisms (-308G>A and -238G>A), and TNF-α serum levels with the susceptibility to gastric precancerous (PL) and GC. Methods:Patients suffering from gastric lesions (65 chronic gastritis, 50 PL, 40 GC) related to H. pylori ‎infection , and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNF-α gene promoter sequencing and TNF-α serum levels are measured by ELISA quantitative method. Results:Regarding TNF-α-308 G/A locus, we noticed higher risk for GC (OR=4.3, CI 1.5-11.9, p-value=0.005) and PL (OR=3.4, CI 1.2-9.2, p-value=0.01) for individuals with AA/GA genotypes compared to GG genotype. Concerning TNF-α-238 G/A locus, we noticed higher risk for GC (OR=5.9, CI 1.2-27.5, p-value=0.01) and PL (OR=4.8, CI 1.3-18, p-value=0.01) for individuals with GG genotype compared to AA/GA genotypes. We noticed that TNF-α serum levels have been increased together with gastric lesions severity. Moreover, TNF-α-308 and TNF-α-238 A alleles seemed to, respectively, upregulate and downregulate TNF-α serum levels. Conclusion:The TNF-α -308 A allele has a promotive effect for GC progression, whereas the TNF-α -238 A allele has a protective function against GC progression. High levels of TNF-α seemed to be associated with the aggressiveness of gastric lesions. TNF-α gene polymorphisms and TNF-α serum levels might be helpful to select those patients who are at high risk for GC.

Study of TNF-α, IFN-γ, TGF-β, IL-6, and IL-10 gene polymorphism in individuals from the leprosy endemic area in the Brazilian Amazon

This study aimed to verify the relationship between the polymorphisms of the cytokines TNF-α rs1800629; IFN-γ rs2430561; TGF-β rs1982073 e rs1800471; IL-6 rs180079 e IL-10 rs1800896, rs1800871 and rs1800872 and leprosy. Blood samples were analyzed from 106 individuals, of whom 24 were paucibacillary (PB), 28 were multibacillary (MB), 32 intradomiciliary consanguineal contacts of patients (CCOSI) and 22 intradomiciliary non-consanguineal contacts of patients (CNCOSI). Analysis of cytokine polymorphisms typified by the polymerase chain reaction (PCR) technique. For TGFβ, a tendency to associate the presence of the C allele at rs1982073 with leprosy was demonstrated, with the T allele being most frequently found in the CCOSI (p = .056). For the polymorphisms IL-10 we found an association of the GCC/GCC genotype with the susceptibility to the disease and the A-allele rs1800896 with the leprosy protection. Greater predominance was found of ACC / ATA (31.3%) and GCC / ATA (37.5%) (p = .03) and the A-allele rs1800896 (76.85%) (p = .043) in the CCOSI groups, while the GCC/GCC was found in the MB group (22.2%) (p = .05). For the other cytokines's SNPs there were no associations with susceptibility to leprosy.These results are limited by sample size, may not be conclusive and will need further confirmation in a larger cohort.

0274 Associations of TNFα Gene Polymorphism with Resilience to Sleep Deprivation and Caffeine Sensitivity

Abstract Introduction Sleep deprivation degrades the fidelity of human brain information processing, leading to cognitive impairment. Carriers of the A allele of a single nucleotide polymorphism of the TNFα gene (G308A, rs1800629) have been found to be resilient to cognitive impairment due to sleep deprivation as compared to individuals homozygous for the G allele. Caffeine mitigates the cognitive impairment associated with sleep deprivation. We investigated whether the effects of caffeine and TNFα genotype interact. Methods In an 18-day, controlled, in-laboratory study, 12 healthy adults (age 27.4±6.9; 6 females) underwent three sessions of 48-hour total sleep deprivation (TSD), with each TSD session preceded and followed by three nights of baseline and/or recovery sleep (10 hours time in bed). In randomized, counterbalanced, double-blind, placebo-controlled fashion, during each TSD session a specific dose of caffeine (0, 200, or 300 mg) was administered four times at 12-hour intervals. Vigilant attention was measured every 2 hours during each TSD session with a psychomotor vigilance test (PVT), for which the log of the signal-to-noise ratio (LSNR) derived from the RT distribution was determined as a measure of the fidelity of information processing. Each subject’s TNFα genotype was assessed from a blood sample. Results Subjects homozygous for the TNFα G allele showed greater PVT impairment during sleep deprivation in the 0 mg caffeine (i.e., placebo) condition as compared to carriers of the A allele and as compared to the 200 and 300 mg caffeine conditions (mixed-effects ANOVA, genotype by dose interaction: F2,566=5.23, p=0.005). There was no appreciable caffeine-related difference in performance for carriers of the A allele, who were relatively resilient to TSD regardless of caffeine dose. Conclusion These results suggest non-additive, interacting effects of TNFα genotype and caffeine and a potentially shared mechanism of action with regard to the fidelity of information processing during sleep deprivation. Support This research was supported by ONR. AJB, TJB, VFC, RHR were supported by DoD MOMRP-USAMRDC. The views expressed here are those of the authors and do not represent the official policy or position of the DoD.

Association between the IL-6, IL-10, and TNFα gene polymorphisms and preterm-birth in Korean women.

Preterm birth (PTB) is a major adverse pregnancy outcome and largely contributes to increasing neonatal and maternal mortality. Genetic and environmental factors may play an important role in the development of PTB. Numerous studies have shown that immune genes related to the immune system, such as IL-6, IL-10, and TNFα, are associated with the occurrence of PTB. We examined genetic associations between IL-6 rs1800796, IL-10 rs1800872, and TNFα rs1800630 polymorphisms and PTB in Korean women. In this study, 115 PTB patients and 147 controls were analyzed. The genotyping of three SNPs was performed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Our result showed that the rs1800872 polymorphism was significantly associated with the development of PTB in genotype frequency (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.01-2.90, p = 0.046). We also found a significant association in an analysis of combined genotypes (rs1800796 CC, rs1800872 CA, and rs1800630 CA) (OR 7.43, 95% CI 2.06-26.84, p = 0.001). In a correlation analysis, rs1800630 A allele was significantly related with the increased birth weight (g) within PTB patients (p = 0.005). Our results imply possible relationships between the rs1800796, rs1800872, and rs1800630 polymorphisms and the development of PTB.

IFN-γ and TNF-α Gene Polymorphisms in Multiple Sclerosis Patients in Northwest Iran.

Cytokines are polypeptides that play critical roles in immune responses. Gene polymorphisms occurring in the inflammatory cytokines are taking a role in autoimmune diseases, including multiple sclerosis (MS), which may induce inappropriate immune responses. The aim of this study was to investigate the allelic and genotypic frequencies of interferon gamma gene (IFN-γ) at +874A/T locus and tumor necrosis factor (TNF-α) at+308A/G locus in MS patients of Azeri population. At first, a questionnaire was prepared for each of 240 healthy, non-relative, and 152 Azeri MS patients before obtaining the blood sample from all subjects. After DNA extraction, the frequency of alleles and genotypes of the IFN-γ and TNF-α genes at +874A/T and -308G/A loci, respectively, were determined by allele-specific PCR method. Finally, the frequencies were compared between control and MS patients by chi-square test (x2-test) and p<0.05 was considered significant. In the IFN-γ +874A/T gene single nucleotide polymorphism (SNP), the most allelic and genotypic frequencies in MS patients were the A allele, 55.26% (p=0.04) and the AT genotype, 52.63% (p=0.048). In healthy individuals, it was 65.42% for the A allele and 45.42% for the AA genotype. For the TNF-α 308 G/A SNP, the highest allelic and genotypic frequencies in MS patients were the G allele with 55.92% (p<0.001) and AG genotype with 61.84%, and in healthy subjects, the allelic and genotypic frequencies were 84.2% and 70.8% for the G allele and GG genotype, respectively. Head trauma, the infection with the herpes virus and Mycoplasma pneumonia, frequent colds and high consumption of canned foods provide grounds for MS. The T allele in the IFN-γ gene (+874) and the genotypes of AA and AG at the TNF-α gene (-308) at the position-308 were considered as potential risk factors for MS. Therefore, the polymorphisms in cytokine genes and following changes in their expression levels can be effective in susceptibility to MS.

Association of IL-1β, IL-6, TNF-α, and TGFβ1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome.

Recurrent spontaneous abortion (RSA) is a common pregnancy-associated complication of polycystic ovary syndrome (PCOS) which is an endocrine malfunction disease. Patients with PCOS may have several underlying contributing and interrelated factors, which have been reported in women with RSA. The incidence rate between PCOS and RSA remains uncertain. The aim of this study is to determine the possible association of IL-1β-511C/T, IL-6-174G/C, TNF-α-1031T/C, and TGFβ1-509T/C with RSA patients with or without PCOS. A total of 140 RSA patients, 70 of which were PCOS patients, and 140 healthy females with no history of RSA or PCOS were included in this study. PCR amplification, genotyping, and sequence analysis were employed to investigate the presence of the polymorphisms. The genotypic and allelic frequencies were calculated separately for each subject. Out of the four studied polymorphisms, the IL-1β-511C/T genotype in RSA without PCOS patients (12.7%) was significantly different compared with that in control subjects (p = 0.047). For IL-6-174C/G, there was a tendency towards more CC carriers among RSA with PCOS patients (10%) than in controls (3%). The GG genotype in RSA women with PCOS (60%) was significantly different compared with that in control subjects (p = 0.033), and the GC genotype in RSA with PCOS patients (30%) showed a marginal significant difference compared with that in control subjects (p = 0.050). Significant difference was identified in the allelic frequencies in RSA patients with PCOS compared to controls (p = 0.025). IL-6-174G/C and TNF-α-1031T/C polymorphisms are significantly associated with RSA patients in Saudi patients with PCOS, while the IL-1β-511C/T polymorphism is significantly associated with RSA patients without PCOS.

Evaluation of TNF-\u03b1 genetic polymorphisms as predictors for sepsis susceptibility and progression

BackgroundThe goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome.MethodsWe performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset.ResultsTNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34–0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21–0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock.ConclusionsTNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

TNF-α gene polymorphism in Iranian Azeri population

BackgroundTumor necrosis factor (TNF-α) is one of the major cytokines in the immune system that plays a major role in the inflammation in the body. The single nucleotide polymorphism (SNP) in the gene of this cytokine at position −308A/G that occurs in the promoter affects its expression level and subsequently predisposes to some malignancies and diseases. This study was conducted to investigate the TNF-α gene polymorphism at position −308A/G in the Azeri population. Material and methodsBlood samples were collected from 240 healthy and non-relevant Azeri individuals. After DNA extraction, the frequency of TNF-α gene genotypes and alleles at -308A/G was determined by allele specific-PCR method. Then comparisons between allele frequencies and TNF-α genotypes with other populations were performed using chi-square test and P value of <0.05 was considered significant. ResultsThe frequency percentage of GG, AG and AA genotypes in TNF-α cytokines at -308A/G in Azeri population was 70.8%, 26.7% and 2.5%, respectively. The frequency percentage of G and A alleles were 84.2% and 15.8%, respectively. The occurrence of TNF-α allele A at -308A/G is associated with high expression of this cytokine. ConclusionThe frequency of AA genotype was much lower than the other two genotypes, with low prevalence observed in other populations, which had a significant association with many diseases and even cancer; therefore, there was no significant difference with most studies examining the polymorphism of this cytokine in the same position.

Association Analysis of Tumor Necrosis Factor Alpha Promoter Polymorphisms and Vitiligo Susceptibility in South Indian Tamils

Tumor necrosis factor alpha (TNF-α) has been associated with the pathogenesis of several autoimmune diseases. Also, various studies in different ethnics showed an association between TNF-α gene polymorphisms and susceptibility to vitiligo. The paucity of genetic data led us to undertake this study to evaluate the association of five TNF-α SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) with the development of vitiligo in South Indian Tamils. A total of 264 vitiligo patients and 264 healthy controls were recruited and TNF-α genotyping was performed using amplification-refractory mutation system polymerase chain reaction and TaqMan allele discrimination assay. Circulatory TNF-α levels were measured by enzyme-linked immunosorbent assay. We observed that a single polymorphic allele A in the promoter region -308 (rs1800629) conferred significant risk to develop vitiligo (p = 0.0002, OR = 1.70, 95% CI = 1.28–2.25), whereas the other polymorphisms failed to contribute to disease risk (p > 0.05). From the constructed haplotypes, TCCAG was found to be a significant risk factor for vitiligo (p < 0.05). Also, a strong linkage disequilibrium was observed between the following SNPs: (1) rs1799964 and rs1800629 (2) rs1800630 and rs1799724 (D’ = 0.90). Analysis of the influence of genotype on phenotypes revealed that the A allele of rs361525 was a risk factor for vitiligo in females (p = 0.04, OR = 0.45, 95% CI = 0.21–0.95), whilst the rs1800629 allele conferred protection against early disease onset (p < 0.05). A statistically significant difference in plasma TNF-α levels was found between cases and controls (p < 0.05). The TNF-α -308A allele and TCCAG haplotype were identified as genetic risk factors for vitiligo susceptibility in South Indian Tamils.

Association between tumor necrosis factor-alpha gene rs1800629 (-308G/A) and rs361525 (-238G > A) polymorphisms and prostate cancer risk in an Iranian cohort.

Prostate cancer (PCa) as the first men's common cancer in the world and the third cancer in Iranian men is a heterogeneous disorder which sometimes several biopsies are needed for its diagnosis. The aim of current study is finding new biomarkers in order to diagnose of PCa at the earliest possible stage. Hence, the relationship between rs1800629 and rs361525 polymorphisms of TNF-α gene with PCa was investigated. Blood DNA samples were collected from 100 patients with PCa, 110 with BPH, and 110 controls. Collected samples were examined using PCR-RFLP and Tetra-ARMS-PCR techniques to detect the desired polymorphisms. The frequency of rs1800629 genotypes in smokers was significantly different from non-smokers with PCa (p= 0.001). Logistic regression analysis results showed that GA heterozygotes in comparison to GG homozygotes had higher risk of developing Benign Prostatic Hyperplasia (BPH) or prostate cancer. However, no significant correlation was considered between the risk of PCa and the TNF-α gene polymorphisms (rs1800629 and rs361525). Although, the achieved results of this investigation demonstrated that the two examined genetic variants do not seem to be suitable markers for early diagnosis of prostate cancer in this pilot study; however increased risk for the disease is shown in GA heterozygotes and smokers which is indicative of some epigenetic factors influence on prostate cancer etiology.

Association of tumor necrosis factor-\u03b1 gene polymorphisms and coronary artery disease susceptibility: a systematic review and meta-analysis

BackgroundThe goal of this study was to review relevant case-control studies to determine the association of tumor necrosis factor-α (TNF-α) gene polymorphisms and coronary artery disease (CAD) susceptibility.MethodsUsing appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through April 2019 were considered for inclusion. Based on eligible studies, we performed a meta-analysis of association between 308G/A, 238G/A, 857C/T, 863C/A and 1031 T/C polymorphisms in TNF-α and risk of CAD.ResultsWe found 25 studies that were consistent with this meta-analysis, including 7697 patients in the CAD group and 9655 control patients. TNF-α 308G/A locus A showed no significant association with CAD susceptibility by the five models in the analysis of the overall population, European, African, South Asian, and North Asian patients. TNF-α 863C/A locus A and 1031 T/C locus C exhibited no significant association with CAD susceptibility. TNF-α 238G/A locus A had no significant association with CAD susceptibility in the overall population. However, TNF-α 238G/A locus A showed significant association with higher CAD susceptibility in the subgroup of Europeans and north Asians. TNF-α 857C/T locus T had no significant association with CAD susceptibility in the analysis of the overall population and Europeans. In the north Asian population, TNF-α 857C/T locus T was associated with lower CAD susceptibility by the heterozygote model.ConclusionTNF-α 308G/A, 857C/T, 863C/A, and 1031 T/C has no significant association with CAD susceptibility. TNF-α 238G/A locus A has significant association with CAD susceptibility in Europeans and north Asians, but has no significant association in the overall population. Studies with a larger sample size are required to confirm the association between TNF-α 238G/A and CAD susceptibility.

Association Between the -1031 (T/C) Polymorphism of TNF-α Gene and Biochemical Factors in Women With Polycystic Ovary Syndrome

Background: Tumor Necrosis Factor Alpha (TNF-α) gene, as an inflammatory factor, plays an important role in reproductive physiology, especially in women with Polycystic Ovary Syndrome (PCOS). Objective: This study aims to investigate the relationship between the -1031 T/C polymorphism of TNF-α gene and biochemical factors in women with PCOS. Methods: In this case-control study, participants were 106 women with PCOS and 114 healthy women referred to Kosar Hospital in Qazvin, Iran. The TNF-α gene’s polymorphism was determined using Polymerase Chain Reaction (PCR) technique and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Biochemical factors of serum levels were also measured in two groups. Logistic regression analysis examined the relationship between the frequency of alleles in different states and the risk of PCOS. Findings: There were statistically significant difference in the mean levels of total cholesterol, triglycerides, testosterone, two-hour blood glucose and body mass index between the groups, whose values were higher in women with PCOS compared to healthy women (P&lt;0.001). In women with PCOS, the mean serum levels of triglyceride and high-density lipoprotein were significantly different between the three TT, CC, TC genotypes of TNF-α gene polymorphism (P&lt;0.05). The results of regression analysis showed that the TT genotype had significant association with the risk of PCOS (OR=2.43, P=0.006, 95%CI: 1.28-2.62). Conclusion: It seems that there is a relationship between the -1301 (T/C) polymorphism of TNF-α gene and the risk of PCOS in women.