TNF-α Gene Polymorphisms Research Articles

Polymorphism of the IL1α, TNFα, IL6 genes and increased ability of neutrophils to form extracellular traps as a predisposing factor in the development of active pulmonary tuberculosis

Objective. To assess the prevalence of IL1α (rs1800587), TNFα (rs1800629), IL6 (rs1800795) gene polymorphisms and the ability of neutrophils to form extracellular traps in patients with active pulmonary tuberculosis (TB). Material and methods. The study included 412 people, divided into 2 groups: main (n=184) – patients with active tuberculosis process who were treated in an inpatient setting at the Clinical Tuberculosis Dispensary (Omsk); control (n=228) – patients infected with Mycobacterium TB, without an active tuberculosis process, and without a history of TB. Results. Analysis of loci rs1800587 of the IL1α gene and rs1800795 of the IL6 gene did not reveal statistically significant differences when assessing susceptibility to the development of active forms of pulmonary TB. The A/A allelic variant of the rs1800629 locus of the TNFα gene was dominant among patients with active TB (p=0.28). An increased ability to form neutrophil extracellular traps was observed in patients with active pulmonary TB. Conclusion. Probably, the revealed increased ability of neutrophils to form extracellular traps is a consequence of the prevalence of TNFα gene polymorphism and the cytokine profile caused by it

Association of the Genotype of TNFα with the Efficiency of the Intensive Phase of Chemotherapy and Formation of the Sizes of Destruction Cavities in Patients with Pulmonary Tuberculosis.

The interrelation between the TNFα gene polymorphism and the effectiveness of the intensive phase of chemotherapy in patients with pulmonary tuberculosis, as well as the formation of diameter of the sizes of destruction cavities was studied. It was revealed that the most adverse course of the disease and a high frequency of formation of destruction cavities are associated with the GG genotype of the TNFα gene.

Gene Polymorphism Of TNF-A (Rs1799964) In Aborted Women With Respiratory Disease In Al-Diwaniyah Province

Background: TNF-α, a proinflammatory cytokine, plays a significant role in the etiology of various illnesses. The encoding gene is found on chromosome 6's short arm in the major histocompatibility complex class III region. Polymorphisms in the TNF-α gene promoter region are believed to impact illness susceptibility and severity. This review summarizes the research on the association between TNF-α gene and receptor polymorphisms and respiratory illness development. This study aim to determine of gene polymorphism of TNF-α in aborted women with respiratory diseases. Methods : The study was carried out for 100 pregnant women, including 60 aborted women with and without respiratory diseases, and 40 women as healthy control group. Genotypes in TNF-α T>C SNPs were identified using self- designed nested T-ARMS PCR tests. Sequencing validated randomly chosen PCR results that represented unique genotypes in TNF-α SNPs. Results : The results of TNF-α (rs1799964) C/T SNP genotyping between aborted women with respiratory diseases and healthy control revealed that the heterozygous C/T genotype was a significant risk factor with an OR of 6.28, while the homozygous TT genotype was non-significant (OR= 2.09). Conclusion : The rs1799964 TNF-α polymorphisms are possible genetic risk factors of respiratory diseases and might be its predictive markers.

Inflammatory Biomarkers in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Faction.

To verify the relationship between gene polymorphisms of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) with inflammation markers and codependent metabolic variables in patients with type 2 diabetes mellitus and chronic heart failure (CHF). This study included 154 patients (mean age, 69.1±3.2 years). The control group consisted of 47 patients with metabolic syndrome (MS) without CHF; the 2nd group included 56 patients with CHF with preserved ejection fraction (CHFpEF); and the 3rd group consisted of 51 patients with CHF with reduced ejection fraction (CHFrEF). The rs1800629 polymorphism of the TNF-α gene (TNF-α: G308A) was studied in real time by the polymerase chain reaction (PCR) method and the rs1800795 polymorphism of the IL-6 gene (IL-6: 174 G>C) was studied by PCR with the electrophoretic detection. The frequencies of polymorphic alleles were compared with the clinical blood test results, plasma concentrations of C-reactive protein (CRP), TNF-α, leptin, and fibrinogen. Differences between the groups were determined using the F test. Relationships between individual studied parameters were identified using the regression analysis. In most patients, the occurrence of gene polymorphisms was eident as increased plasma concentrations of biomarkers. An association was found between the TNF-α gene polymorphism (G308A) and an increase in plasma TNF-α and between the IL-6 gene polymorphism (174 C>G) and an increase in plasma CRP. In the CHFpEF group, the rs1800629 gene polymorphism was observed in 55% of patients, among whom 93% had increased TNF-α. The rs1800795 gene polymorphism was observed in 82% of CHFpEF patients, among whom 21% had increased CRP. In the CHFrEF group, the G308A transition in the TNF-α gene was observed in 53% of patients; an increase in the respective cytokine was noted in 67% of patients; the IL-6 gene polymorphism 174 C>G was found in 78%, however, only 14% of patients with this polymorphism had also increased CRP. In the control group, the TNF-α G308A gene polymorphism was found in 30% of patients, while an increase in free TNF-α was associated with this polymorphism in 50% of patients; the IL-6 174 C>G gene polymorphism was detected in 78%, while no increase in the CRP level was observed in this group. This demonstrates a high probability of the TNF-α G308A gene polymorphism occurrence in patients with CHF. Inflammatory markers are important predictors of CHF. The most significant predictor was the TNF-α G308A gene polymorphism, which was observed in more than 50% of patients, the majority of whom had an increase in plasma TNF-α.

The evaluation of IL-4 VNTR intron 3 and TNF-α (rs1799964) gene polymorphisms in Egyptian patients with alopecia areata: a case–control study

BackgroundAlopecia areata (AA) is a non-scarring hair loss condition that usually affects the scalp. The exact pathogenesis is poorly understood; however, multiple factors like genetics, environmental, psychological, and immunological factors may have a role. The purpose of this study was to look into possible links between the functional interleukin-4 (IL-4) gene intron 3 variable number of tandem repeats (VNTR) and TNF-(rs1799964) gene polymorphism and AA susceptibility. This case–control study consisted of 79 unrelated patients and 156 age- and sex-matched healthy individuals as a control group. The Severity of Alopecia Tool was used to assess the extent of hair loss from the scalp. Polymerase chain reaction (PCR) with specific primers was used to determine IL-4 gene 70-bp VNTR polymorphism while polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) was used to investigate TNF-α (rs1799964) gene polymorphism.ResultsNone of the selected polymorphisms for both genotypes and alleles had statistical significance when patients and controls were compared with each other (p-values for IL-4 VNTR were 0.11, 0.74, 0.052 and 0.27 and for TNF-α polymorphism was 0.71, 0.43, 0.65 and 0.55, respectively, for codominant, dominant, recessive and overdominant models of inheritance, respectively). Furthermore, the same results were retrieved when the genotypes were compared with the patient’s clinical and demographic data (p-value > 0.05).ConclusionThe findings indicate that IL-4 VNTR intron 3 and TNF-α (rs1799964) gene polymorphisms are not linked to the development of AA in the Egyptian population.

Predicting the risk of developing vibration disease and vegetative-sensory polyneuropathy under vibration exposure using analysis of candidate gene polymorphism

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

Прогнозирование риска развития вибрационной болезни и вегетативно-сенсорной полинейропатии при вибрационном воздействии с исполь-зованием анализа полиморфизма кандидатных генов

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

Assessment of TNF-α (-857 C/T) gene polymorphism in oral lichen planus disease: A case-control study.

Oral lichen planus (OLP) is an inflammatory mucocutaneous disorder with an immune-mediated pathogenesis. The tumor necrosis factor-α (TNF-α) level in the serum of OLP patients is significantly higher than in the control group. TNF-α-857 C/T polymorphism can be related to the increased TNF-α level in blood circulation. This study investigated the relationship between TNF-α (-857 C/T) polymorphism and OLP patients in an Iranian population. Saliva samples were taken from 200 people, including 100 patients with OLP and 100 healthy people who did not have significant differences in age and sex. Then, DNA was extracted from them and the TNF-α (-857 C/T) genotype was identified using the polymerase chain reaction with confronting two-pair primers method. Statistical Package for the Social Sciences version 16 software analyzed the results. The frequency of C/C, C/T, and T/T genotypes of the TNF-α-857 C/T polymorphism in the patient group were 78%, 18%, and 4%, respectively, and in the control group were 72%, 23%, and 5%, respectively. The differences between the two groups regarding allele (χ 2 = 0.97, p = 0.32) and genotype (χ 2 = 0.96, p = 0.62) frequency among the studied population were insignificant. This study showed that the difference in the frequency ofsingle nucleotide polymorphism TNF-α-857 C/T polymorphism in the patient and control group had no significant relationship with the increased OLP incidence. Also, no significant association was observed between allele and genotype frequency of TNF-α (-857 C/T) with OLP subtypes.

An Investigation on the Correlation Between Diabetic Foot Infection, Osteomyelitis, Venous Insufficiency, and IL-6 (-174 G>C) and TNF-α (-238 G>A) Gene Polymorphisms

An Investigation on the Correlation Between Diabetic Foot Infection, Osteomyelitis, Venous Insufficiency, and IL-6 (-174 G>C) and TNF-α (-238 G>A) Gene Polymorphisms

Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-β, IL-1R1 and IL-R antagonists might be involved in the GT progression.

Polymorphism of CSN2 and TNF-α Genes in the Population of Holstein Cattle Bred in Ukraine

Polymorphism of CSN2 and TNF-α Genes in the Population of Holstein Cattle Bred in Ukraine

Association of IL-10–592 C > A /-1082 A > G and the TNFα -308 G > A with susceptibility to COVID-19 and clinical outcomes

BackgroundVariation in host immune responses to SARS-CoV-2 is regulated by multiple genes involved in innate viral response and cytokine storm emergence like IL-10 and TNFa gene polymorphisms. We hypothesize that IL-10; -592 C > A and − 1082 A > G and TNFa-308 G > A are associated with the risk of SARS-COV2 infections and clinical outcome.MethodsGenotyping, laboratory and radiological investigations were done to 110 COVID-19 patients and 110 healthy subjects, in Ismailia, Egypt.ResultsA significant association between the − 592 A allele, A containing genotypes under all models (p < 0.0001), and TNFa A allele with risk to infection was observed but not with the G allele of the − 1082. The − 592 /-1082 CG and the − 592 /-1082/ -308 CGG haplotypes showed higher odds in COVID-19 patients. Severe lung affection was negatively associated with − 592, while positive association was observed with − 1082. Higher D-dimer levels were strongly associated with the − 1082 GG genotype. Survival outcomes were strongly associated with the GA genotype of TNFa. -308 as well as AGG and AAA haplotypes.ConclusionIL-10 and TNFa polymorphisms should be considered for clinical and epidemiological evaluation of COVID-19 patients.

Polymorphism of Rs1800629 Gene of TNF-Α in the Pathogenesis of Acne Vulgaris

Background: The study of the association between acne vulgaris and the TNF-gene polymorphism rs1800629 in the Uzbek population is discussed in this article. Methodology: The research was conducted on 165 patients with various clinical forms of acne vulgaris and 161 healthy donors. Findings: During this research, allele frequencies and genotypes of rs1800629 polymorphism of TNF-α gene were found with statistically significant differences between the control group and subgroups of patients with acne vulgaris. As a result of the investigation, it was discovered that heterozygous genotype G/A should be a genetic marker for an increased risk of acne development, whereas homozygous genotype G/G should be a marker for a reduced risk of acne formation.

Quantitative assessment of the association between TNF-α gene polymorphisms and angina risk.

Previous investigations into the correlation between tumor necrosis factor-α (TNF-α) gene polymorphism and susceptibility to angina have produced a range of results. This study aims to clarify the potential significance of TNF-α polymorphism as a contributing factor to the onset of angina. A comprehensive review of all corresponding literature was conducted across several major databases, covering their records from inception through to March 2024. Data were synthesized using meta-analysis techniques. Notable associations were identified in various genetic comparisons: allele contrast (A vs. G: OR=0.77, 95% CI=0.70-0.86, P<0.001), homozygote comparison (AA vs. GG: OR=3.35, 95% CI=2.51-4.48, P<0.001), heterozygote comparison (GA vs. GG: OR=1.69, 95% CI=1.19-2.40, P=0.003), recessive genetic model (AA vs. GG/GA: OR=2.40, 95% CI=1.91-3.03, P<0.001), and dominant genetic model (AA/GA vs. GG: OR=1.84, 95% CI=1.27-2.65, P=0.001). Furthermore, ethnicity-based subgroup analyzes revealed that these associations were especially significant within the Asian population and unstable angina, with all genetic models demonstrating statistical significance (P<0.05). TNF-α gene is significantly associated with an increased risk of angina, particularly among the Asian population and unstable angina. This finding underscores the importance of considering genetic factors in the assessment and management of angina risk.

Study of TNF-α, IFN-γ, IL-10, TGF-β and IL-6 Gene Polymorphisms in a Cohort of Professionals Who Worked in the First Pandemic Wave in the Brazilian Amazon

Study of TNF-α, IFN-γ, IL-10, TGF-β and IL-6 Gene Polymorphisms in a Cohort of Professionals Who Worked in the First Pandemic Wave in the Brazilian Amazon

Influence of IL-10, IL-6 and TNF-α gene polymorphism on obesity.

Obesity is one of the most serious public health issues. Obesity is caused by a complex interaction of genetic, metabolic, social, cultural, and environmental variables. Obesity prevalence in both children and adults has risen substantially in recent years, and the condition is now considered an epidemic. Forty-two obese males with BMI≥ 30 were included in this study. Their age interval was (16-45) years. Controls include 42 males with normal BMI≤25 and age group (16-45) years were selected. Serum level and single nucleotide polymorphism were determined for IL-10, IL-6 and TNF-α. For evaluating gene polymorphism, the allele was counted by direct allele counting. The Hardy-Weinberg equilibrium was assessed with the χ2-test. In IL-10 the GA genotype was found about 5th folded than controls with (OR:4.71, C.I:1.86 to 11.91). IL-6 genotype GG was revealed as an etiologic factor and GC as a protective factor for obesity. While for TNF-α the GG genotype was protective and GA was a risk factor for obesity. Point mutation in G/A for IL-10 and TNF-α were considered as developing factors, whereas the GG genotype was etiologic to obesity in this study.

Tumor necrosis factor alpha gene polymorphism affects the pattern of idiopathic nephrotic syndrome in Kuwaiti Arab children.

TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases, but its association with idiopathic nephrotic syndrome (INS) is poorly understood. This study looked for an association of TNF-α gene polymorphisms with INS, as well as its effect on steroid responsiveness among Kuwaiti Arab children. Genotypes of the TNF-a gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism in 151 INS Kuwaiti Arab patients and 64 age and sex-matched controls. Clinical data of all subjects were reviewed. The heterozygous AG genotype was detected in 8.6% of INS patients compared 23.4% of the controls (p < 0.01). Comparing steroid responsiveness, AA genotype was significantly more common in steroid-sensitive nephrotic syndrome (SSNS) cases than steroid-resistant nephrotic syndrome (SRNS) patients (p = 0.001). However, AG genotype was significantly more common in SRNS patients compared to the SSNS cases (p = 0.001). No difference was found between these two subgroups in the GG genotype frequency. AG genotype of TNF-a gene polymorphisms may be considered a suitable marker for INS disease among Kuwaiti children. Both AA and AG genotypes may be useful in predicting steroid responsiveness among these cases of Arab ethnicity. The findings might open the era for the use of genetic markers in the early treatment of NS.

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN-RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV-HCV and HCV-HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.

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.