Tumor Necrosis Factor-alpha Polymorphisms Research Articles

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 < 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 < 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 polymorphisms in the TNFA, TNFRSF1A and TNFRSF1B genes with lepromatous leprosy in Western Mexican patients.

Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.

A Comprehensive Integration of Data Regarding the Correlation of TNF-α rs1800629 Polymorphism with Susceptibility to Cervical Cancer.

Cervical cancer, globally, ranks as the runner-up among the most prevalent forms of cancer affecting women. The role of the tumor necrosis factor alpha (TNF-α) polymorphism in the susceptibility to cervical cancer has been a subject of interest. However, the current evidence regarding this association remains inconclusive. To address this uncertainty, eligible studies were systematically searched and retrieved from various databases including Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, and Wanfang database. The search was conducted until September 01, 2023. The collected literature was then subjected to independent analysis by two authors. The pooled odds ratio along with the corresponding 95% confidence interval was calculated using different genetic models. Additionally, sensitivity and cumulative analyses were performed to assess the stability of the obtained results. A total of 29 case-control studies involving 8850 cases and 9286 controls were included in the present analysis. The findings revealed that the TNF-α rs1800629 polymorphism increased the risk of cervical cancer under the allele genetic model (A vs. G: OR = 1.277, 95% CI = 1.104-1.477, P = 0.001) in the general population. Subgroup analysis based on ethnicity demonstrated that this polymorphism was associated with an increased risk of cervical cancer in Caucasian and African women, but not in Asians. Furthermore, subgroup analysis based on country of origin indicated a significant correlation between the TNF-α rs1800629 polymorphism and an increased risk of cervical cancer in American and Chinese women, but not in Iranian women. The findings from this meta-analysis suggest that the TNF-α rs1800629 polymorphism is a risk factor for cervical cancer in the general population, particularly in Caucasian and African women. However, further well-designed studies are warranted to validate these findings.

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.

Tumor Necrosis Factor-Alpha (+489 G/A) Polymorphism Can Predict the Response to Adalimumab in Chinese Han Patients With Ankylosing Spondylitis.

Studies investigating the association between single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and the efficacy of adalimumab (ADA) in ankylosing spondylitis (AS) therapy have reported conflicting results. We aimed to investigate the value of SNP typing of TNFα in predicting the efficacy of ADA in AS. Eighty patients with active AS who received ADA treatment were followed up for 24 weeks. Six known SNPs of TNFα (+489G/A, -238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were subjected to the SNaPshot SNP typing method, which has been proven to be a reliable, efficient, and cost-effective method for detecting SNPs. The relationship between each SNP genotype and the therapeutic efficacy of ADA was analyzed. At the end of the 24-week follow-up, 58.8% of the patients with AS achieved Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR), 67.5% of the patients achieved the criteria of an ASAS40response (40% improvement on indices), and 53.8% of the patients achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement (MI). The univariate analysis showed that patients with AS carrying the TNFα +489 A allele were more likely to achieve ASAS-PR, ASAS40 response criteria, and ASDAS-MI after ADA treatment. In the multivariate regression analysis, the TNFα +489 A allele was an independent factor influencing the efficacy of ADA in treating AS (ASAS-PR odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.01-7.01; ASAS40 OR = 4.56, 95% CI = 1.39-15.00; ASDAS-MI OR = 3.31, 95% CI = 1.02-10.69). The patients carrying the TNFα +489 A allele may be more likely to experience better therapeutic efficacy and achieve the treatment target (ASAS-PR, ASAS40 response, or ASDAS-MI) after receiving ADA treatment. Detection of TNFα +489 G/A may predict the therapeutic efficacy of ADA, which can be used in clinical practice to tailor treatment for individual patients with AS. Further studies with larger sample sizes and longer follow-up periods with imaging evaluation are needed to verify our findings.

Association between tumor necrosis factor-alpha polymorphisms (rs361525, rs1800629, rs1799724, 1800630, and rs1799964) and risk of psoriasis in studies following Hardy-Weinberg equilibrium: A systematic review and meta-analysis

ObjectivePsoriasis is a disease with an immunogenetic background in which cytokines have important effects on its prevalence and incidence. The present meta-analysis evaluated the relationship between tumor necrosis factor-alpha (TNF-α) polymorphisms (rs361525, rs1800629, rs1799724, 1800630, and rs1799964) and psoriasis risk in studies following Hardy-Weinberg equilibrium (HWE). Materials and methodsFour databases were searched to retrieve relevant studies reporting the distributions of TNF-α polymorphisms in psoriasis cases compared to controls. The effect sizes were the 95% confidence intervals (CIs) and odds ratios (ORs). Subgroup analysis, sensitivity analyses, publication bias, trial sequential analysis (TSA), and meta-regression were performed on the initial pooled results of TNF-α polymorphisms. ResultsThirty-six articles with 71 studies were included in the meta-analysis (twenty-six: rs361525, twenty-seven: rs1800629, nine: rs1799724, four: 1800630, and five: rs1799964). The pooled ORs for −238 G/A rs361525 polymorphism were 2.33 (p < 0.00001), 2.79 (p < 0.0001), 2.35 (p < 0.00001), 2.44 (p < 0.00001), and 2.45 (p < 0.00001), as well as 1.57 (p < 0.00001), 1.98 (p = 0.01), 1.61 (p < 0.00001), 1.64 (p < 0.00001), and 1.79 (p < 0.00001) for −857 C/T rs1799724 polymorphism in allelic, homozygous, heterozygous, dominant, and recessive models, respectively. Ethnicity, psoriasis type, and sample size affected the pooled results of rs361525, rs1800629, and rs1799724 polymorphisms. Based on TSA, there were just sufficient cases for −238 G/A rs361525 polymorphism in five genetic models and −857C/T rs1799724 polymorphism in allelic, heterozygous, and dominant models. ConclusionsThe A allele and GA and GG genotypes of −238 G/A rs361525 polymorphism and T allele, TT and CT genotypes of −857C/T rs1799724 polymorphism were related to increased risks in psoriasis cases. Well-designed studies (with no deviation from HWE in controls) with more cases are recommended in the future.

The Association of Genetic Polymorphisms in Tumor Necrosis Factor-Alpha and Interleukins with Disease Severity or Response to Biological Therapy in Iraqi Rheumatoid Arthritis Patients: A Narrative Review

Background: Tumor necrosis factor-alpha (TNF-α) and interleukins play important roles in the pathogenesis of rheumatoid arthritis (RA). Genetic research has been employed to find many of the missing connections between genetic risk variations and causal genetic components. Objective: The goal of this study is to look at the genetic variations of TNF-α and interleukins in Iraqi RA patients and see how they relate to disease severity or response to biological therapy. Method: Using specific keywords, the authors conducted a systematic and comprehensive search to identify relevant Iraqi studies examining the genetic variations of TNF-α and interleukins in Iraqi RA patients and how they relate to disease severity or response to biological therapy. Results: Thirteen studies have looked at TNF-α and interleukin genetic polymorphisms in Iraqi RA patients. Only the IL-2, IL-4, IL-6, IL-17, and IL-23 receptor gene polymorphisms were explored for interleukins; however, the results of studies indicate no association between genetic polymorphism and the severity of RA. Very few researchers examine the correlation between genetic variation and TNF-α inhibitor responsiveness. Numerous studies have been conducted to investigate the genetic variations of the TNF-α promoter. The -308 G/A region in the promotor region was the most studied location.

A glaucoma-associated OPTN polymorphism, M98K sensitizes retinal cells to endoplasmic reticulum stress and tumour necrosis factor α.

Optineurin/OPTN polymorphism, M98K is associated with normal tension glaucoma in certain populations, and genetic evidence shows its interaction with tumour necrosis factor-alpha (TNFα) polymorphism in causing glaucoma. Endoplasmic reticulum (ER) stress is also associated with glaucoma. We hypothesized that M98K-OPTN may sensitize retinal ganglion cells to various types of stress. To test this hypothesis, stable clones of a retinal cell line, 661W, expressing either wild-type (WT)-OPTN or M98K-OPTN were generated and examined for their survival under various stress conditions. Compared with WT-OPTN expressing cells, M98K-OPTN expressing cells showed significantly lower cell survival and higher activation of caspase-3 and caspase-8 upon treatment with tunicamycin (an inducer of ER stress) or TNFα. Levels of ER stress sensors IRE1α, PERK and ATF6 were significantly higher in M98K-OPTN expressing cells. Tunicamycin treatment resulted in significantly higher induction of ER stress marker CHOP and several other ER stress response genes regulated by IRE1α-XBP1, PERK-ATF4 and ATF6 pathways, in M98K-OPTN expressing cells. Splicing of XBP1 and ATF6 activation was higher in tunicamycin-treated M98K-OPTN expressing cells. Increased levels of PERK and IRE1α proteins in M98K-OPTN expressing cells were dependent on autophagy. Overall, our results show that M98K-OPTN sensitizes retinal cells to TNFα and ER stress-induced cell death. We also show that M98K-OPTN alters ER stress response signalling, which possibly enhances the sensitivity of retinal cells to ER stress. Our results provide support to the hypothesis that M98K-OPTN may cooperate with other genetic or environmental factors to cause retinal ganglion cell death associated with glaucoma.

Association between interleukin-1, interleukin-6, and tumor necrosis factor-alpha polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

In juvenile idiopathic arthritis (JIA), interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are associated with development and progression of JIA. We investigated whether IL-1, IL-6, and TNF-α polymorphisms were associated with susceptibility to JIA. A meta-analysis was conducted on the associations between IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA (PubMed and Embase). A total of 27 studies involving 4678 JIA patients and 7634 controls were considered in the meta-analysis. There was no association between the IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA in allele contrast or any other genetic models. In subgroup analysis based on subtype, except for the dominant model of TNF-α-238 G/A, systemic JIA was not significantly associated with IL-6 and TNF-α polymorphisms. In Caucasians, the dominant and additive models of IL-1β-511 C/T were significantly associated with JIA (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.09-2.00, P=0.01; OR 1.46, 95% CI 1.05-2.03, P=0.02, respectively). This meta-analysis showed no association between IL-1, IL-6, and TNF-α polymorphisms, and JIA, but the TT genotype of IL-1β -511 C/T was associated with higher prevalence of JIA in Caucasians.

Interaction between Single Nucleotide Polymorphisms (SNP) of Tumor Necrosis Factor-Alpha (TNF-α) Gene and Plasma Arsenic and the Effect on Estimated Glomerular Filtration Rate (eGFR).

When poisons enter the human body, tumor necrosis factor (TNF-α) will increase and cause damage to tissues through oxidative stress or inflammatory reaction. In previous studies, arsenic (As) has known to cause many health problems. Some studies have shown that As exposure is negatively correlated with estimated glomerular filtration rate (eGFR), or with the prevalence of proteinuria. At present, there are few studies focusing on the effects of As exposure and TNF-α single nucleotide polymorphism (SNP) to eGFR; thus, this study was intended to explore the interactions between TNF-α SNPs and plasma As and their effects on eGFR. A cohort of 500 adults, aged 30 to 70 years, was randomly selected from Taiwan Biobank (TWB). We used the gene chip to screen out seven SNPs of the TNF-α gene and used the results, combined with questionnaires, biochemical tests, and stored plasma samples from the TWB, for the analysis of As by inductively coupled plasma mass spectrometry (ICP-MS). After adjustments for BMI, hypertension, hyperlipidemia, kidney stones, and smoking habits, multiple regression statistics were performed to explore the interaction between SNPs and plasma As with eGFR. In this sample of the general population, plasma As had a significant association with the decline of eGFR (β (SE) = −7.92 (1.70), p < 0.0001). TNF-α gene SNP rs1800629 had the property of regulating TNF-α, which interacts with plasma As; individuals with the AG type had a significantly lower eGFR than those with the GG type, by 9.59 mL/min/1.73 m2 (p < 0.05), which, regarding the dominant model, could infer that the A allele is a risk allele. SNP rs769177 had no interaction with plasma As; however, participants with the TT or TC type had significantly higher eGFR levels than the CC carriers, by 4.02 mL/min/1.73 m2 (p < 0.05). While rs769176 interacted with plasma As, if a person with the TC type had a higher plasma As concentration, that would sustain higher eGFR. This study found that certain SNPs of the TNF-α gene would be robust to the decline of eGFR caused by As exposure. Still, we need further research to confirm the protective regulation mechanism of these SNPs.

Role of tumor necrosis factor-alpha–308 G/A and interleukin-10 promotor–592 C/A polymorphisms in adult immune thrombocytopenic purpura

Introduction: Immune thrombocytopenia (ITP) pathogenesis has been related to cytokine imbalance, which is controlled genetically with gene polymorphisms. The correlation of the interleukin (IL)-10 gene and tumor necrosis factor alpha (TNF-α) polymorphisms with ITP susceptibility has been previously investigated, but the association with clinical and prognostic parameters remains unclear. Material and methods: To investigate the relation between IL-10-592 C/A and TNF-α-308 G/A gene polymorphisms and their clinical significance in adult patients with ITP. This study was conducted on 40 ITP patients and 40 control individuals. The IL-10-592 C/A polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method and the TNF- α-308 G/A polymorphism by amplification refractory mutation system analysis. Results: The TNF-α-308 G/A polymorphism was significantly associated with low platelet count, wet purpura, higher bleeding score, higher incidence of complications, and lack of response to steroid therapy. The IL-10-592 C/A polymorphism was not significantly associated with any of these parameters. Conclusion: We found a significant association between the TNF-α-308 G/A polymorphism and several clinical parameters, which suggests a probable role in the prognosis among adult ITP patients.

Association Between TNF-α-308, +489, -238 Polymorphism, and COPD Susceptibility: An Updated Meta-Analysis and Trial Sequential Analysis.

The tumor necrosis factor alpha (TNF-α) polymorphism may play an important role in chronic obstructive pulmonary disease (COPD) susceptibility. However, the results are still inconclusive. Eligible studies were searched in Cochrane Library database, EMBASE, Pudmed, Web of science, China National Knowledge Infrastructure, and Wanfang database. Finally, a total of 27 case-control studies with 3473 COPD cases and 4935 controls were included in the present analysis. We also performed trial sequential analysis (TSA) to confirm our results. Overall, association between TNF-α-308G/A polymorphism and COPD susceptibility was identified in allelic model (A vs. G, OR = 1.21, 95%CI: 1.01–1.45, p = 0.04) when smoking status was not adjusted. In ethnicity subgroup analysis, we found that the TNF-α -308G/A polymorphism was associated to COPD among Asians (GA vs. GG, OR = 1.35, 95%CI: 1.04–1.77, p = 0.02) when smoking status was not adjusted. However, no significant association was found in Asian smokers or Caucasian smokers. In conclusion, our study suggest that TNF-α-308 GA genotype is related to COPD in the Asian population. In addition, the TNF-α+489G/A, - 238G/A variants do not increase the risk of COPD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021273980.

Contribution of -1031T/C and -376G/A tumor necrosis factor alpha polymorphisms and haplotypes to preeclampsia risk in Tunisia (North Africa)

Preeclampsia is a gestational disorder characterized by hypertension and proteinuria. Excessive release of pro-inflammatory cytokines, particularly tumour necrosis factor-alpha, has been demonstrated to contribute to endothelial activation and poor trophoblast invasion in placental development, resulting in preeclampsia's clinical symptoms. Genetic polymorphisms of tumour necrosis factor-alpha can regulate its production and may play an important role in the pathogenesis of this disease. This study aimed to evaluate the association of five tumour necrosis factor-alpha gene promoter single nucleotide polymorphisms, or their haplotype combinations, with preeclampsia prevalence. This case-control study was conducted on 300 women with preeclampsia and 300 age-matched women with normal pregnancy from Tunisian hospitals. Genotyping of tumour necrosis factor-alpha −1031 T/C, −376 G/A, −308 G/A, −238 G/A, and +489 G/A SNPs was performed on DNA extracted from blood samples using PCR-restriction fragment-length polymorphism analysis. Statistical analysis was performed using the chi-square test. P < 0.01 were considered statistically significant to take into consideration the multiple comparisons. A significantly higher frequency of the minor allele -1031C (p < 0.001) was observed in preeclampsia cases compared to controls. Notably, the -1031C and -376A (CA) haplotype, which correlates with a higher production of TNF-α protein, had a higher incidence in women with preeclampsia (p = 0.0005). Conversely, the TG haplotype had a low frequency in preeclampsia cases compared to controls (p = 0.002) which suggests that it is associated with a reduced incidence of preeclampsia. These results suggest that tumour necrosis factor-alpha polymorphisms, in particular the -1031C/A, and the haplotype CA, contribute to an increased risk of preeclampsia in Tunisian women.

BIRD FANCIER'S DISEASE: A CASE OF HYPERSENSITIVITY PNEUMONITIS

TOPIC: Occupational and Environmental Lung Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: The immunologic lung disease through inhalation and sensitization of an aerosolized antigen is termed hypersensitivity pneumonitis (HP). Here we describe a case of HP from exposure to avian antigen. CASE PRESENTATION: A 42 y/o F presented with progressively worsening dyspnea at rest & exertion, pleuritic chest pain, dry cough for past 2 months. She denied sick contacts or recent travel. On exam BP: 122/76mmHg, HR 107bpm, RR 30bpm, SpO2 82% on room air. Physical exam, significant for b/l crackles. Labs: WBC 16.33 k/mm3, ABG PaO2 of 45mmHg. CXR showed b/l airspace opacities & CT-thorax showed b/l diffuse GGO. ECHO showed LVEF 55% with normal global systolic function with mildly elevated PASP. Treatment was initiated with hi-flo oxygen and her SpO2 improved to 97%. QuantiFERON Gold, urine legionella, Mycoplasma IgM, and respiratory multiplex viral panel were negative. Cardiac CT revealed patent coronaries. Spirometry revealed severe restrictive ventilatory defect. Further questioning revealed that patient got parakeets a few months prior to onset of symptoms. She was then started on methylprednisolone for possible HP. Bronchoscopy with BAL and transbronchial biopsies showed no bacterial/fungal/viral growth. Cytology was unremarkable and biopsies revealed mild inflammatory changes with lymphocytes and aggregates of intralaveolar foamy macrophages. The CD4:CD8 ratio was 0.89. Patient clinically improved with steroid therapy and gradually weaned from supplemental oxygen. She was discharged on oral prednisone with close follow up where she continued to improve after removal of her parakeets DISCUSSION: HP an immune-mediated response from repeated inhalation, sensitization, & hyperresponsiveness to various organic particles which can be mammalian or avian proteins, fungi, bacterial, or chemicals. Based on duration of exposure & symptoms onset, HP can be divided into acute, subacute, or chronic. Acute HP presents as flu-like illness, subacute HP has insidious onset of symptoms, dyspnea on exertion or reduced exercise capacity. Physical exam reveals inspiratory crackles. Imaging usually demonstrates GGO, mosaic attenuation and centrilobular nodules. BAL reveals lymphocytic predominant cells with CD8 alveolitis. Histopathology usually demonstrates cellular bronchiolitis with predominant lymphocytic or plasmocytic infiltrates. It can also present as interstitial mononuclear infiltrates or loosely-formed granulomas. Treatment for HP is avoidance of antigen exposure. Role of steroids in treating HP is not well known, however general practice is slow tapering steroid regimen for about 3-6 months duration. Prognosis is usually good with complete recovery in most patients; a few may progress to chronic fibrosing HP. CONCLUSIONS: A high level of suspicion should be present in diagnosing HP with a thorough history and prompt management must be initiated to prevent progression of disease. REFERENCE #1: Selman M, Pardo A, King TE Jr. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Is J Respir Crit Care Med. 2012; 186:314-24. REFERENCE #2: Costabel U, Bonella F, Guzman J. Chronic hypersensitivity pneumonitis. Clin Chest Med. 012; 33:15163. REFERENCE #3: Camarena A, Juárez A, Mejía M, Estrada A, Carrillo G, Falfán R, Zuñiga J, Navarro C, Granados J, Selman M. Major histocompatibility complex and tumor necrosis factor-alpha polymorphisms in pigeon breeder's disease. Am J Respir Crit Care Med. 2001;163:1528-33. DISCLOSURES: no disclosure on file for Jagadish Akella; No relevant relationships by Alex Diaz, source=Web Response no disclosure on file for Iqbal Javed; No relevant relationships by Raghavendra Sanivarapu, source=Web Response

Time-Specific Associations of Tumor Necrosis Factor-α Levels and Polymorphisms (-850 C/T or -308 G/A) With Suicidal Ideation in Acute Coronary Syndrome Patients.

Background: Considering the association of inflammation with suicide and acute coronary syndrome (ACS), we investigated the individual and interactive effects of serum tumor necrosis factor-alpha (sTNFα) levels and two polymorphisms (−850 C/T and −308 G/A) on suicidal ideation (SI) after ACS.Methods: The SI status using items on the Montgomery–Åsberg Depression Rating Scale (MADRS), related covariates including sociodemographic and clinical characteristics, sTNFα levels, and tumor necrosis factor-alpha (TNF-α) polymorphisms were evaluated in 969 patients within 2 weeks after ACS. Of the patients, 711 were evaluated 1 year later for SI. Multivariate logistic regression models were used to calculate individual and interactive associations after adjusting for the covariates.Results: Higher (vs. lower) sTNFα levels and the −850 C/T or T/T (vs. C/C) polymorphism were significantly associated with SI 2 weeks after ACS, while only higher sTNFα levels were significantly associated with SI after 1 year. Significant interactive effects were detected between sTNFα (higher) levels and the −850 C/T (C/C or C/T) polymorphism on SI 2 weeks after ACS and between the two (−850 CC or CT and −308 G/A or AA) polymorphisms on SI 1 year after ACS.Conclusions: The sTNFα level and two polymorphisms (−850C/T and −308 G/A), separately or in combination, could be time-specific biomarkers for SI in ACS. Focused interventions for ACS patients at risk of SI might reduce the suicidal burden in patients with ACS.

Association of tumor necrosis factor-α (−308 G/A) and interleukin-10 (−1082 A/G) gene polymorphisms with polycystic ovary syndrome in Iraqi women

BackgroundThe etiologic factors of polycystic ovary syndrome (PCOS) are not well understood, however, several studies reported that genetics and environmental factors might be involved in the appearance of PCOS. Therefore understanding some molecular pathways can provide more information about PCOS. The imbalance of pro-inflammatory and anti-inflammatory cytokines could be associated with its pathophysiology. There are huge numbers of polymorphisms within cytokine genes that may affect their production and bring in the women more susceptible for PCOS. The aim of the present study was for evaluation the correlation of single nucleotide polymorphism (−308 G/A) in tumor necrosis factor-alpha (TNF-α) gene and (−1082 A/G) in interleukin-10 (IL-10) gene with PCOS. MethodsPatients group included 80 women who had a history of PCOS diagnosed using transvaginal or transabdominal ultrasound and don't have any of the inherited disorders such as androgen-secreting neoplasms, congenital adrenal hyperplasia, thyroid dysfunction, and hyperprolactinemia with a mean age (27.23 year). The control group included 70 women with a mean age (26.89 year). Levels of serum IL-10 and TNF-α in woman with PCOS and healthy control have been measured by Enzyme linked immunosorbent assay (ELISA). Single nucleotide polymorphism (SNP) in TNF-α (−308 G/A) and IL-10 (−1082 A/G) genes and the frequency of mutations in patient and control group were evaluated using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). ResultsShowed that serum IL-10 concentration was significantly decreased (p < 0.01) while TNF-α level was significantly increased (p < 0.01) in patients compared to control group. While the genotype prevalence of TNF-α (−308 G/A) and IL-10 (−1082 A/G) and the allele frequency show non-significant difference (p > 0.05) between women with PCOS and healthy controls. ConclusionIt is concluded that the level of TNF–α and IL-10 could be considered as possible biomarkers for PCOS while polymorphisms in IL-10 gene and TNF-α gene are not considered as risk factors of PCOS in Iraqi women, this suggests that further studies on other loci or other cytokines are required.

Tumour necrosis factor-alpha polymorphism -308 G/a and its protein in subjects with gingivitis

Objective This study examined the association between tumour necrosis factor-alpha (TNF- α) (–308 G/A) polymorphism and gingivitis, and serum and salivary TNF- α levels, in a Mexican population. Material and methods This study enrolled 171 subjects, divided into two groups: healthy subjects and gingivitis patients. TNF- α (–308 G/A) gene polymorphism was analyzed by PCR-RFLP assay. Salivary and serum samples were used to measure cytokine levels through the ELISA technique. Results TNF- α (–308 G/A) polymorphism was shown to have a protective effect in carriers of the A/A genotype and allele A. The G/A genotype is associated with an increase in high-density lipoprotein cholesterol (HDL-C) levels in the gingivitis group. Healthy individuals had higher levels of salivary TNF- α and HDL-C, and increased salivary flow. Triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels were increased in the gingivitis group. No statistical differences were found in serum TNF- α levels. Conclusion Our data demonstrate that the TNF- α −308 A/A genotype exerts a protective effect against gingivitis. Moreover, oral conditions are associated with some biochemical parameters.

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 at verifying the relationship between the polymorphisms of the cytokines tumor necrosis factor-alpha (TNF-α) -308 G → A (rs1800629); interferon gamma (IFN-γ) +874 T → A (rs2430561); transforming growth factor-beta (TGF-β) códon 10 (rs1982073) and códon 25 (rs1800471); interleukin (IL)-6 - 174 G → C (rs180079) and IL-10 - 1082 A→T (rs1800896); -819 C → T (rs1800871); -592 A→C (rs1800872); and leprosy. Blood samples were analyzed from 106 individuals, of whom 24 were paucibacillary (PB), 28 were multibacillary (MB), and 54 were patient contacts. Analysis of cytokine polymorphisms was typified by the polymerase chain reaction technique. For TGF-β +869 T → C and +915 G→C, a tendency to associate the presence of the C allele at codon 10 with leprosy was demonstrated, with the T allele being most frequently found in the CCOSI (P = 0.056). For the polymorphisms IL-10 - 1082 A→T, -819 C→T, and -592 A→C, we found an association of the GCC/GCC genotype with the susceptibility to the disease and the A allele at position 1082 with the leprosy protection. Greater predominance was found of ACC/ATA (31.3%) and GCC/ATA (37.5%) (P = 0.03) and the A allele at position -1082 (76.85%) (P = 0.043) in the CCOSI groups, whereas the GCC/GCC was found in the MB group (22.2%) (P = 0.05). For the other cytokines's single-nucleotide polymorphisms, 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.

Association between tumor necrosis factor alpha and lymphotoxin alpha gene polymorphisms and migraine occurrence among Jordanians.

Inflammatory reactions in the body have been shown to contribute to migraine development. Therefore, genes involved in the inflammatory pathways might play a role in the susceptibility and development of migraine. In this study, polymorphisms in tumor necrosis factor alpha (TNFα) and lymphotoxin alpha (LTA) genes were tested for association with migraine. A total of 398 participants (198 migraine patients and 200 controls) were recruited in the study. Serum TNF level was measured using a sandwich ELISA kit. Lymphocytes' and monocytes' counts were obtained from a differential complete blood count profile. Participants' DNA was extracted and genotyped for rs1800629 and rs1799724 in TNFα, and rs909253 in LTA. Controls had a significantly higher mean lymphocyte count (P = 0.018), while the mean monocyte count and serum TNFα levels did not differ between the two groups (P > 0.05). With respect to gene polymorphisms, the rs1800629 and rs1799724 variants showed significant association with migraine in all subjects, and in males and females when analyzed separately (P < 0.001). The rs909253 did not show any statistical difference in frequencies among the two groups (P > 0.05). Having the A allele in rs1800629 was associated with a higher risk of migraine in both male (OR, 95%; CI, G/A = 3.79 [1.87-7.69]; A/A = 14.22 [1.67-121.14]; P < 0.01) and female (OR, 95%; G/A = 2.54 [1.47-4.38]; A/A = 2.52 [1.12-5.69]; P < 0.001) subjects. In conclusion, rs1800629 and rs1799724 in TNFα showed significant association with migraine among the Jordanian population.

Genetic Polymorphism of Tumor Necrosis Factor-Alpha, Interferon-Gamma and Interleukin-10 and Association With Risk of Mycobacterium Tuberculosis Infection.

Background. Mycobacterium tuberculosis has become the leading cause of morbidity and death in humans worldwide. Thus, genetic variability of the host plays a major role in human susceptibility to the pathogen, among others. Therefore, the objective of this finding was to assess the association of genetic polymorphisms of cytokines with tuberculosis infection.Method.A cross-sectional study was conducted between January and May 2018. Five ml of whole blood was collected and extracted the genomic DNA through simple salting out method. The patterns of genetic polymorphism were determined by amplification refractory method PCR using specific primers. Finally, the PCR run on electrophoresis of agarose gel and the band was visualized under UV light. A logistical regression model has been adapted to assess the association of genetic polymorphisms with tubercular infection. In order to determine the association between the explanatory and outcome variable, the odds ratio with 95% CI was calculated. P < 0.05 is a statistically significant value.Result.In present study, the frequency of TNF-α -308 G allele and GG genotype OR (95% CI)= 0.20 (0.11-0.37), and OR (95% CI)= 0.29 (0.18-0.46)), respectively) and IFN-γ +874 A allele and AA genotype OR (95% CI)= 3.80 (2.11-6.86) and (OR (95% CI)= 1.61(1.13-2.28), respectively) were significantly associated with tuberculosis incidence. In contrast, there is no significant correlation between IL-10 -1082 A and AA of allele and genotype, respectively in tuberculosis patients (p > 0.05) was evident.Conclusion.From our finding, the genetic variability of TNF-α -308 A and IFN-γ +874 alleles are the potent host genetic risk factors associated with tuberculosis infection.