TNF-α Polymorphisms Research Articles

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.

Genetic association between TNFA polymorphism rs1799964 with a more severe course of idiopathic inflammatory myopathies

Genetic association between TNFA polymorphism rs1799964 with a more severe course of idiopathic inflammatory myopathies

Correlation of TNF-α polymorphisms with susceptibility to lung cancer: evidence from a meta-analysis based on 29 studies

ObjectiveThis meta-analysis aims to clarify the association between the TNF-α -308G > A and − 238G > A polymorphisms and lung cancer risk.MethodA comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P < 0.05 considered statistically significant. All analyses were performed using Comprehensive Meta-Analysis (CMA) 2.0 software.ResultsThe analysis included 19 case-control studies with 3,838 cases and 5,306 controls for the TNF-α -308G > A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the − 238G > A polymorphism. The − 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the − 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002).ConclusionThe − 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the − 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor.

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.

THE SIGNIFICANCE OF GENE POLYMORPHISM OF SOME PRO- AND ANTIINFLAMMATORY CYTOKINES IN PATIENTS WITH SEVERE ULCERATIVE COLITIS

The objective of the study was too study the polymorphism of TNFa(rs1800629), IL10(1800871, 1800896) ITGA4(rs1143674, rs1449263), ITGB7(rs11574532) genes in patients with severe ulcerative colitis (UC) Materials and methods. The study included 70 people with UC who lived in the Irkutsk region, the Republic of Buryatia and the Zabaikalsky krai. Patients were divided into two groups: patients receiving genetically engineered biological therapy (GIBT; n = 22) and patients receiving basic therapy (n=48). The control consisted of 115 healthy volunteers. The genotypes were studied by real-time PCR. For statistical processing, we used the criterion χ2, the odds ratio (OR), binary logistic regression analysis with the calculation of 95% confidence interval (CI) using the program "IBM SPSS Statistics Version 25.0". Results. Homozygotes of ITGA4(rs1449263)GG had 2.5 times higher chances of developing the disease than carriers of other polymorphic variants (OR = 2,580; 95% CI: 1,129-5,898; χ2 = 5,266; p = 0,022). Patients with extracellular manifestations (ECM) were 3 times more likely to receive GIBT (OR = 3,000; 95% CI: 0,982-9,167; χ2 = 3,878; p = 0,049). IL10 media(1800896)AA prevailed in the group of patients receiving basic therapy (OR = 0,282; 95% CI: 0,089-0,890; χ2 = 5,473; p = 0,020). Subjects with the homozygous variant of ITGA4(rs1143674)CC were 3.5 times more likely to have indications for the administration of GIBT (OR = 3,536; 95% CI: 1,077-11,603; χ2 = 4,576; p = 0,033). The results of binary logistic regression demonstrated that the homozygous genotype of ITGA4(rs1143674)CC and extraintestinal manifestations of the disease were predictors for an unfavorable prognosis of UC accompanied by the GIBT administration. Conclusion. The association of the debut of the disease, smoking, polymorphic variants TNFa(rs1800629), IL10(1800871), ITGB7(rs11574532) with the UC development and clinical manifestations was not revealed. The disease developed 2,5 times faster in homozygote ITGA4(rs1449263)GG than in other genotype carriers. Subjects with polymorphic variant IL10(1800896)AA prevailed in the group of patients with basic therapy. In addition to the previously known extraintestinal manifestations of the disease, the ITGA4 genotype (rs1143674) CC can act as a risk factor for the development of severe UC, requiring the GIBT administration.

Associations between IL-1β, IL-6, and TNFα polymorphisms and longitudinal trajectories of cognitive function in non-demented older adults

Inflammation is implicated in Alzheimer's disease (AD), and specific single nucleotide polymorphisms (SNPs) in inflammatory cytokine genes are associated with increased AD risk. Whether the same polymorphisms also predict domain-specific cognitive change in cognitively healthy older adults is unclear. Specific SNPs in three cytokine genes, IL-1β (rs16944), IL-6 (rs1800795), and TNFα (rs1800629) were assessed for association with longitudinal trajectories spanning up to 16 years of global cognitive function, episodic memory, attention and working memory, and executive function in a sample of 324 non-demented older adults. Only rs1800629 (TNFα) was associated with significant change in global cognitive function over time [γ = 5.22; 95% CI: 0.61, 9.83; p = 0.027]. Despite an association with AD risk, rs16944 and rs1800795 may not predict cognitive decline in cognitively healthy older adults. The presence of an A at rs1800629 (TNFα) may have broad, protective effects on cognitive function, over time. More validation studies are needed to determine whether specific cytokine SNPs are associated with respective serum levels to further understanding of AD biomarkers that may also serve as markers of cognitive decline.

Tumor necrosis factor‑α ‑308 G/A genetic polymorphism in patients with chronic obstructive pulmonary disease presenting with hyperactive airways.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. COPD is often diagnosed late in the disease leading to a delay in management. Notably, tumor necrosis factor-α (TNF-α) polymorphisms may serve an important role in the development of COPD. A single-center, case-control study was conducted to determine the presence of the TNF-α -308 G/A polymorphism among patients diagnosed with COPD presenting with hyperactive airways, patients without COPD presenting with hyperactive airways, and normal study participants without pulmonary comorbidities. Three genotypes: G/G (94%; 157/167), G/A (5%; 9/167) and A/A (1%; 1/167) were detected by quantitative PCR. The present study showed that the presence of the TNF-α -308 G/A polymorphism reduced the odds of having hyperactive airways with COPD by 29.3% and hyperactive airways without COPD by 26.3%. Multinomial logistic regression analysis showed that having the TNF-α -308 G/A polymorphism did not significantly reduce the odds of having hyperactive airways with COPD and without COPD compared to those with the G/G genotype. In conclusion, the presence of the TNF-α -308 G/A gene polymorphism showed no significant association with patients with COPD with or without hyperactive airways. The presence of the TNF-α -308 G/A polymorphism instead had a weak association with the reduction in the development of COPD regardless of the presence or absence of airway hyperactivity.

Tumor necrosis factor-α polymorphism and risk of primary nephrotic syndrome: A case-control study and meta-analysis.

The current study aims to explore the relationship between tumor necrosis factor-α (TNF-α) polymorphism and the risk of primary nephrotic syndrome (PNS). A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF-α polymorphism were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. In addition, a meta-analysis was conducted to analyze previously published literature on this topic. No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta-analysis results revealed a positive association between TNF-α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). TNF-α rs1800629 polymorphism does not appear to confer any increased risk for PNS.

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.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Association of polymorphic variants of cytokines genes, endothelial growth factor and matrix metalloproteinases with the development of uterine fibroids among russian women

One of the factors in the development of uterine fibroids is a genetic predisposition to its occurrence in some women, but the real molecular genetic mechanisms of this phenomenon remain unknown. Aim of the study was the distribution analysis of gene polymorphism of cytokines TNFα, IL-1β, IL-4, IL-6, IL-10, factors of angiogenesis (vascular endothelial growth factor, VEGF) and remodeling of extracellular matrix (metalloproteinases MMP2, MMP3, MMP9), which are associated with their levels. Material and methods. Genotyping was performed by real-time PCR using commercial test systems SYBR GreenI (Litech, Russia) and TaqMan (Syntol, Russia) in accordance with the instructions of the developer. Cytokine content in blood serum was determined by flow cytometry using microspheres coated with monoclonal antibodies to cytokines (Bio-Plex ProTM Human Cytokine 27-plex Assay), according to the instructions for Bio-Plex 200 (Bio-Rad Laboratories, USA).To evaluate the results obtained, in addition to the generally accepted methods of statistical processing for case – control studies, computational methods of bioinformatics were used for comparative analysis of the diagnostic value of various combined genetic traits. Results. It was shown that the maximum odds ratio value of uterine fibroids development are combined genetic traits that include representatives of all four regulatory factors: cytokines with pro-inflammatory activity, cytokines with anti-inflammatory activity, vascular endothelial growth factors and metalloproteinases (p = 0.002). Conclusions. The presented data reveal the real mechanisms of manifestation of the genetic predisposition of individual women to the uterine fibroids development, associated with the presence of polymorphism of certain genes in their genome, which provide features of the structure of cytokine networks with the predominance of certain activities in the regulation of tissue processes in the uterus. In addition to purely scientific interest, these results indicate the real possibility of their clinical application in the form of prognostic criteria with a certain level of prognostic significance.

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.

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.

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.

Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients.

Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

Rs1800629 polymorphism in TNF-alpha is associated with the susceptibility and initial short-term glucocorticoids efficacy in myasthenia gravis patients

Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory agent involved in various autoimmune and inflammatory diseases including myasthenia gravis (MG). In this study, we enrolled 409 adult MG patients and 487 healthy individuals to investigate the association between TNF-α polymorphism and MG. We found the rs1800629 A allele frequency was significantly higher in the MG group than in the control group. Subgroup analysis revealed that the A allele frequencies were significantly higher in the early-onset subgroup, non-thymoma subgroup, ocular-onset subgroup, and mild severity subgroup than in the control group. To minimize the interactions between clinical features, we used a comprehensive classification and found that the rs1800629 A allele frequency was significantly higher in the non-thymoma AChR-Ab negative subgroup than in the control group. In the analysis of initial short-term glucocorticoids (GC) efficacy in the treatment-naive patients, the rs1800629 A allele frequency was significantly higher in the unresponsive subgroup than in the responsive group and the control group. Logistic regression demonstrated the rs1800629 genotypes in the dominant model and disease duration prior to GC treatment independently contributed to initial short-term GC efficacy. In conclusion, our study revealed that in Chinese adult MG patients, rs1800629 polymorphism in TNF-α was associated with the susceptibility of MG and might indicate the initial short-term GC efficacy.

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.

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.

Cervical cancer risk in association with TNF-alpha gene polymorphisms in Bangladeshi women.

Tumor necrosis factor-alpha (TNF-α) is among the vital pro-inflammatory cytokines that potentially exerts a significant influence on the immune response, hence potentially regulating the advancement of cervical lesions. Our study objective was to examine the relationship between two single nucleotide polymorphisms (SNPs) (rs1799724 and rs1800629) of TNF-α and the risk of cervical cancer in women from Bangladesh. We recruited 133 patients with cervical cancer and 126 healthy individuals for this study. Genotyping was performed using real-time PCR SNP genotyping assay. Multivariate logistic regression analysis was used to determine the odds ratio (OR) along with 95% confidence intervals (CI) and p-values. For rs1799724 (C > T) polymorphism, TT mutant homozygous genotype carried 3.26 times increased risk of developing cervical cancer (OR = 3.26, 95% CI = 1.15-9.28, p = 0.027). Polymorphism of rs1800629 (G > A) was also related to an elevated risk of cervical cancer. Individuals with the AG heterozygous genotype (OR = 2.85, 95% CI = 1.20-6.74, p = 0.017) and AA mutant homozygous genotype (OR = 4.55, 95% CI = 1.24-16.60, p = 0.022) also had a higher likelihood of having cervical cancer. Moreover, we found that injectable contraceptives increase the risk of cervical cancer. Individuals who smoked and/or had first-degree relatives with cancer were more likely to carry the risk allele, which increases the likelihood of developing cervical cancer. TNF-α polymorphisms in rs1799724 and rs1800629 increase the susceptibility of developing cervical cancer in women from Bangladesh.