TNF-α Genotypes Research Articles

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.

Association between tumor necrosis factor-α gene polymorphism and interleukin-6 level with mortality of neonatal sepsis

Sepsis is a systemic infection that significantly causes morbidity and mortality among neonates, which is associated with immature immune response. Variations in the tumor necrosis factor-alpha gene (TNF-α) -308G/A may be linked to neonatal sepsis mortality by modulating interleukins (ILs) involved in the immune response cascade, such as IL-6. The aim of this study was to investigate the association between TNF-α -308G/A gene variation and IL-6 level with mortality of neonatal sepsis. A cohort of 30 neonates diagnosed with clinical sepsis was recruited. Blood culture was performed for all patients and serum IL-6 levels were examined 24 hours after suspected sepsis. Genetic analysis of TNF-α single nucleotide polymorphisms (SNP) -308G/A was conducted using polymerase chain reaction and DNA sequencing. The association was assessed based on bivariate logistic regression. We found that 12 (40%) of 30 patients had blood culture-proven sepsis. Genotype of TNF-α -308G/A stratified of the patients was 56.7% for GA and 43.3% for GG. There were no AA variations found in this study. There was no significant association between the TNF-α -308 G/A genotype and mortality in neonatal sepsis (p=0.211). Similarly, the allelic model of TNF-α -308 gene had no association with mortality (p=0.325). Additionally, there was no association between serum IL-6 level and mortality in neonatal sepsis (p=0.253). In conclusion, SNP of TNF-α -308 gene and IL-6 level are not associated with mortality in neonatal sepsis.

Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study.

The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.

Exploring the Association of Biochemical Characterization and Genetic Determinants of TNF-α, CXCR2, and CCR5 Delta 32 Mutation with Predisposition to Polycystic Ovary Syndrome.

In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics. The case-control study's findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation-including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)-exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant (p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032. Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes.

Evaluation of interleukin-4 and tumor necrosis factor-alpha in patients with breast cancer

Abstract Background: Breast cancer is a complicated, multifaceted condition that affects a wide range of entities and exhibits significant heterogeneity in its clinical, morphological, and molecular characteristics. Objective: This study intended to determine whether there is a correlation between the serum level of IL-4 expression and the single nucleotide polymorphism in tumor necrosis factor-alpha (TNF-α) in the development of breast cancer. Materials and Methods: IL-4 serum levels in 70 patients (35–65 years old) and 70 control groups (30–50 years old) were determined using the enzyme-linked immunosorbent assay (ELISA) technique. Genomic DNA was obtained from blood samples for molecular analysis to investigate the TNF-α-308 G→A gene polymorphism in patients and the control groups. Genotyping done by using tetra amplification refractory mutation system-polymerase chain reaction technique. Results: Patients with breast cancer had significantly higher serum IL-4 levels than the control group (P &lt; 0.001), 133.27 (66.00) vs. 38.66 (38.00), respectively. The frequency distribution of the TNF-α genotype in the patients with breast cancer and control groups was studied. In the patient group, there were 56 out of 70 heterozygous AG genotypes compared to 6 out of 70 in the control group (P &lt; 0.001). With an odds ratio of 37.33 (95% confidence interval: 7.99–174.51) and an etiologic fraction (EF) of 0.88, the AG genotype existed indeed a risk factor. Conclusion: In the current investigation, the heterozygous AG genotype was shown to be substantially more linked with IL-4 serum and TNF-α genotype in breast cancer patient groups. Also, the homozygous GG genotype was significantly higher in correlation between IL-4 serum and TNF-α genotype in breast cancer patient group.

Association of TNFα and IL1β genotypes with the risk of Staphylococcus aureus causing recurrent tonsillitis in a sample of Iraqi patients

Background and aim: Tonsillitis is an inflammation of the tonsils, usually caused by an infection by viruses or bacteria; recurrent tonsillitis occurs when tonsillitis occurs several times a year. The current study aimed to investigate the association of TNFα and IL1β genotypes with the increased risk of recurrent Staphylococcus aureus tonsillitis in a sample of Iraqi patients. Methods: A total of 50 blood samples were collected from patients with recurrent tonsillitis of S. auerus from three hospitals in Najaf city, and 50 samples were collected from apparently healthy volunteers with a free medical history of recurrent tonsillitis as control group. Genomic DNA was extracted from peripheral blood and genotyped for TNF-α 308G/A and IL1β C/T SNP using Nested tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Results: The results of the distribution IL β –rs1143627 C/T alleles in S. aureus tonsillitis patients showed CC wild type genotype was in 11 patients (22%), CT genotype was in 30 patients (60%) and the TT genotype was in 9 patients (18 %) also C allele frequency was (0.42), whilst T allele frequency was (0.58) with Odds Ratio (1.507) at significant difference (P≤ 0.01), while prevalent of TNF-α –rs1800629 G/A alleles genotype in S. aureus tonsillitis patients revealed that GG wild type genotype was 37 patients (74%), GA genotype was 13 patients (26%) and AA genotype was 0(0%) also, G allele frequency was (0.87) and A allele frequency was (0.13) with Odds Ratio (1.507) at no significant differences in both the patient and control.

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.

Toll-like receptor 7 and tumor necrosis factor alpha polymorphisms in Egyptian patients with autoimmune thyroid diseases

ABSTRACT Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) susceptibility depends on a complex interaction between environmental and genetic factors. Genes for tumor necrosis factor alpha (TNF-α) and toll-like receptors (TLRs) have been incorporated into the pathophysiology of autoimmune disorders. Our aim is to assess the association between TLR7 (rs179009) and TNF-α (rs1800629) polymorphisms and susceptibility to autoimmune thyroid disorders. One-hundred ninety-nine individuals, divided into 68 HT patients in group I, 57 GD patients in group II, and 74 age- and gender-matched healthy subjects in group III, underwent laboratory investigations, including the detection of TLR7 and TNF-α polymorphisms using real-time PCR technique. TLR7 (rs179009) genotypes, A/G and G/G, were significantly more prevalent in HT patients (group I) compared to normal controls. Meanwhile, TNF-α (rs1800629) genotypes in GD patients (group II) showed a six fold increase in the risk of the disease in the G/A and A/A genotypes. Our findings propose the fact that the polymorphisms of TLR7 (rs179009) play a role in the susceptibility and the development of Hashimoto’s thyroiditis, whereas TNF-α (rs1800629) polymorphisms play a role in the susceptibility and development of Graves’ disease.

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.

Polymorphism of cytokine and C-reactive protein genes in patients with psoriasis in the Kemerovo region of Russia

Aim. To study the associations of polymorphisms of IL-1b (rs16944), IL-6 (rs1554606), IL-8 (rs2227306), IL-10 (rs1800896), TNFα (rs361525), CRP (rs1205) genes and their intergenic interactions with the risk of psoriasis development in Kemerovo region residents. Materials and Methods. We examined 170 patients (102 men and 78 women) a clinically established diagnosis of vulgar psoriasis. The average age of patients was 46.2+3.9 years, 165 people (97%) had progressive stage psoriasis. The control group (n=155) included 98 healthy men and 57 women matched by age. Genomic DNA isolated from peripheral blood leukocytes by phenol-chloroform extraction according to the standard protocol was used as material. Logistic regression analysis was performed to assess the role of intergenic interactions in the development of psoriasis. Conclusion. In patients of the Kemerovo region, vulgar psoriasis is associated with minor homozygous genotypes of polymorphic variants of TNFα (rs361525), IL-1b (rs16944), CRP (rs1205) genes. The minor homozygous TNFα (rs361525) genotype has a high odds ratio and is determinant in the development of this form of psoriasis among all genes studied. The major allele and IL-10 genotype (rs1800896) is a disease modifier and affects the clinical course, particularly the development of inflammatory plaques and papules on the lower and upper extremities of patients.

Cytokine polymorphisms and genotypic susceptibility of HCV infection in ribavirin response to peg interferon.

Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.

Distribution of polymorphic variants of the TNF-α and TNFRSF1α genes in miners with dust lung pathology

Introduction. Long-term exposure to coal-rock dust on the body causes the development of systemic inflammation, one of the development mechanisms of which is an increase in the production of pro-inflammatory cytokines as follows: TNF-α, IL-1β, IL-2, IL-6. The development and course of occupational pathology were shown to depend on the individual characteristics of the body of those who works in hazardous conditions. In this regard, it is necessary to establish the significance of the polymorphism of the TNF-α and TNFRSF1α genes in the development of dust lung pathology in workers of the main occupations of the mines in the South of Kuzbass. &#x0D; The aim of the study was to investigate the prevalence of polymorphic variants of the TNF-α (rs1800629) and TNFRSF1α (rs4149584) genes in miners with dust lung pathology.&#x0D; Materials and methods. A survey of one hundred twenty seven miners working for a long time in the mines of the south of Kuzbass was carried out. Of these: &#x0D; 69 miners with prolonged exposure to high concentrations of coal-rock dust with a previously proven diagnosis of dust lung pathology, 58 miners without a proven diagnosis of dust lung pathology working in the same sanitary and hygienic conditions (control). The typing of the TNF-α (rs1800629) and TNFRSF1α (rs4149584) genes was carried out using the Real-Time method.&#x0D; Results. The GG rs1800629 TNF-α genotype were shown to be a potent molecular genetic marker of the risk of developing dust lung pathology, the chance of detecting it in the group of the miners with dust pathology is almost 4 times higher than in the control group. The carriage of the A allele and the heterozygous AG rs1800629 TNF-α genotype reduce the probability of developing dust lung pathology. It has been established that the GG rs4149584 TNFRSF1α genotype can be a molecular and genetic marker of the risk of developing dust lung pathology, the chance of detecting it in the group of the miners with dust pathology is 2.6 times higher than in the control group.&#x0D; Limitations. The study was limited by relatively small size of the groups under study.&#x0D; Conclusion. The carriage of homozygous GG genotypes of the rs1800629 and rs4149584 polymorphic loci of the TNF-α and TNFRSF1α genes, respectively, is associated with the risk of developing dust lung pathology in miners in the South of Kuzbass. The carriage of the A allele and the heterozygous AG rs1800629 TNF-α genotype reduce the probability of developing dust lung pathology.

Association of genetic variation in tumor necrosis factor-α gene with susceptibility to rheumatoid arthritis in southern Iraq

: Rheumatoid arthritis is the most commonly occurring systemic autoimmune disease caused by genetic, epigenetic, and environmental factors. It affects 0.5-1% of the worldwide population and increases in incidence with age. Tumor necrosis factor-α, major candidate gene in the pathogenesis of RA. Gene polymorphisms occurring in this pro-inflammatory cytokine may increase the risk of RA. This study aimed to evaluate the association between polymorphisms in TNF-α gene at location -308(rs1800629), -238(rs361525) and -376(1800750) (G/A) and RA susceptibility. The study also evaluated the effects of these polymorphisms on their corresponding gene levels in serum. Methods: This case-control study was conducted on 49 individuals (30 RA patients and 19 age- and sex-matched healthy volunteers as controls). Genomic DNA extracted from all participant blood, then amplified by PCR and genotyped by sequencing.Additionally, the serum level of TNF-α was quantified using an enzyme-linked immunosorbent assay (ELISA). Results: The results showed that thehomozygosity for the TNF-α -308 G allele significantly act as a genetic factor associated with increased RA risk (p = 0.029, OR: 4.727, 95%CI: 1.175–19.016). The A allele of -238 and -376 polymorphisms may act as a possible risk factor for RA (OR: 7.63, 95%CI:0.409-14.07; OR:6.13, 95%CI:.0.32-11.214). However, no significant differences were observed. Conclusion: The GG genotype ofTNF-α -308 SNP associated with increased rheumatoid arthritis risk.

Association of Tumor Necrosis Factor-Alpha (TNF-α) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

Abstract Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-α (TNF-α) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA &gt; Del) and TNF-α (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19). Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups. Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p &lt; 0.05). The GG genotype of the TNF-α was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-α was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold). Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes.

Correlation between ABO Blood Grouping & Allergic Rhinosinusitis with and without Polyposis & Role of TNF-α Polymorphism in Allergic Rhinosinusitis.

The objective of this study was to find distribution of ABO blood group in patients of allergic rhinosinusitis and also to map evidence of the association of TNF-α in different blood groups of patients suffering from allergic rhinitis with or without nasal polyp. Prospective Observational study. Patients with allergic nasal symptoms aged between 18 and 70years attending outpatient department were assessed and eligible patients who gave consent for the study were included. Patients of allergic rhinosinusitis with nasal polyp had higher serum Ig E count as compared to patients without nasal polyp. 97 patients of allergic rhinosinusitis were Rh positive. Allergic rhinosinusitis was most common in blood group O + ve and B + ve. Allergic rhinosinusitis with polyp was most common in B + ve and without polyp was in O + ve. The frequency of GG, GA and AA genotypes of TNF-α (-308) G/A were 40%, 58%, 2%. The frequency TNF-α (-308) GA was maximum in patients of allergic rhinosinusitis with polyp. In patients of allergic rhinosinusitis without polyp TNF-α (-308) GA and GG had equal distribution of patients (48.6%). The frequency of single allele G in both groups was high as compared to allele A. Association of blood group with allergic rhinitis and TNF-α might help clinicians in better understanding and management of patients suffering from allergic rhinitis in future.

Post-COVID Pain Is Not Associated with Inflammatory Polymorphisms in People Who Had Been Hospitalized by COVID-19.

Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, p > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.

Genetic variations of tumor necrosis factor-α and prostaglandin-endoperoxide synthase 2 genes among Egyptian patients with type 2 diabetes mellitus and diabetic nephropathy

ObjectivesThe current study aimed to determine whether genetic differences in the tumor necrosis factor-α (TNF-α) and prostaglandin-endoperoxide synthase 2 (PTG2) genes are linked to type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). BackgroundDN is a major cause of chronic kidney disease (CKD). Unfortunately, the precise pathogenic mechanisms of DN are not completely understood. Recent data suggest a link between inflammatory cytokines and the chronic complications of T2DM. TNF-α and PTG2 are key mediators of inflammation. Subjects and methodsThis is a case-control study that includes 100 patients (group 1: 50 diabetic patients with diabetic nephropathy and group 2: 50 patients without diabetic nephropathy) and 50 age- and sex-matched healthy controls (group 3). Genotyping of TNF-α (rs3651525) and PTGS2 (rs689466) by real-time PCR was applied. ResultsTNF-α (rs3651525) and PTGS2 (rs689466) genotype frequency and allelic distribution are in Hardy-Weinberg equilibrium (HWE). When T2DM patients with nephropathy were compared to those without DN, regression analysis for the PTGS2 rs689466 and TNF-rs361525 single nucleotide polymorphisms (SNPs) demonstrated that none of the SNP genotypes showed a major risk factor for DN susceptibility. As regards TNF-α rs361525, GA and AA genotypes were significantly associated with a higher risk of T2DM when compared to GG, and A allele showed a 3.721-fold increased risk.TNF-α rs361525 AA genotype (OR, 10.980; 95% CI 1.385–87.066) and TNF-rs361525 GA genotype (OR, 3.050; 95% CI 1.315–7.0758) are the most substantially linked parameters with the risk of diabetes mellitus in univariate analysis.According to the multivariate analysis, the AA and GA genotypes of the SNP rs361525 significantly affect the development of diabetes mellitus. No remarkable association was found between the PTGS2 (rs689466) polymorphism and diabetes mellitus and diabetic nephropathy. ConclusionIn contrast to the lack of a significant correlation between PTGS2 (rs689466) and DM or DN, TNF-α rs361525 was connected to the possibility of developing diabetes mellitus in our study.

Differential genotypes of TNF-α and IL-10 for immunological diagnosis in discoid lupus erythematosus and oral lichen planus: A narrative review.

Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians’ understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.

The functional polymorphism -863 C/A in the TNF-α gene is associated with primary open-angle glaucoma development in Iraqi patients

Glaucoma is one of the main causes of irreversible blindness. The most common type of glaucoma is primary open-angle glaucoma (POAG). This study aimed to evaluate the possible association between the −863 C/A TNF-α (tumor necrosis factor-alpha) gene polymorphism and −1562 C/T MMP9 (matrix metallopeptidase 9) gene polymorphisms in POAG. Blood samples from apparently healthy controls and patients (40–70 years) with POAG were taken from Baghdad's Ibn Al-Haitham Teaching Eye Hospital. For detecting TNF-α serum levels in peripheral blood, enzyme-linked immunosorbent assay (ELISA) approaches are utilized. Sequence-specific primers with 3 end mismatches were used to amplify the specific allelic variants of −863 C/A TNF-α by sequence-specific primers -polymerase chain reaction (SSP-PCR). The −1562 C/T MMP9 gene polymorphisms were genotyped by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. The mean TNF-α level was significantly elevated in POAG patients (132.85 ± 5.18 pg/ml, P = 0.001) than in the controls (71.52 ± 2.07). The CC genotype of TNF-α is a risk factor for the development of POAG (56, 74.7 %, OR: 2.3158, 95 % CI: 1.1594–4.6256, p = 0.0174) as compared with CA and AA genotypes. The TNF-α (−863) C allele is a risk factor for POAG development (OR: 2.1095, 95 % CI: 1.2207–3.6452, p = 0.0075). The TNF-α (−863) A allele is protective (OR: 0.4741, 95 % CI: 0.2743–0.8192). The results of MMP9 genotyping reveal that none of the three genotypes (TT, TC, and CC) or the two alleles (T and C) are related to POAG development. In conclusion, High levels of TNF-α are associated with POAG. The CC genotype of TNF-α is a risk factor for the development of POAG as compared with CA and AA genotypes. The TNF-α (−863) C allele is a risk factor for POAG while the TNF-α (−863) A allele is protective. No significant difference among the three genotypes (CC, CT, and TT) with POAG development was observed.

Associations of Tumor Necrosis Factor-Alpha Gene Polymorphisms (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-Alpha Serum Concentration with Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a neurodegenerative disease leading to irreversible central vision loss among the elderly in developed countries. While the disease accounts for 9% of all cases of vision loss, the prevalence of AMD is likely to increase due to the exponential aging of the population. Due to this reason, our study aimed to determine the associations of tumor necrosis factor-alpha (TNF-α) gene single-nucleotide polymorphisms (SNPs) TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-α serum concentration with age-related macular degeneration. Analysis of TNF-α rs1800630, rs1800629, and rs361525 polymorphisms showed that the TNF-α rs1800630 A allele was statistically significantly more frequent in the exudative AMD group compared to the control group (p = 0.029). Additionally, the TNF-α rs1800630 A allele was more frequent in females with exudative AMD than in the control group of healthy females (p = 0.027). The TNF-α rs1800630 A allele was more frequent in females with exudative AMD than in females with early AMD (p = 0.014). TNF-α rs1800630, rs1800629, and rs361525 haplotype A-A-G were associated with decreased odds of exudative AMD (p < 0.0001), and haplotype A-G-G was associated with 24-fold increased exudative AMD occurrence (p < 0.0001). TNF-α protein levels were lower in subjects with exudative AMD compared to the control group (p < 0.001). The study showed significant associations between inflammatory cytokine TNF-α single-nucleotide polymorphisms and serum level with AMD pathogenesis. Analysis of TNF-α genotypes and serum concentration may be helpful for the AMD diagnosis.