TNF Polymorphisms Research Articles

Interaction between polymorphisms in TNF-⍺ and RANKL genes is associated with the development of persistent apical periodontitis, in Brazilian subjects

ObjectivesTo investigate the association between genetic polymorphisms in suppressor of cytokine signaling-1 (SOCS-1), tumor necrosis factor-⍺ (TNF-α) and its receptors 1 and 2 (TNFRSF1A and TNFRSF1B), receptor activator of nuclear factor kappa-b (RANK), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG), and persistent apical periodontitis (PAP). MethodsPatients with pulp necrosis and apical periodontitis at the time of non-surgical root canal treatment were followed up for at least one year. A total of 423 subjects were included, 172 with signs/symptoms of PAP and 251 with apical periodontitis healed. DNA was extracted from saliva and used for genotyping polymorphisms in SOCS1 (rs243327 and rs33977706), TNF-α (rs1800629), TNFRSF1A (rs1800693), TNFRSF1B (rs1061622), RANK (rs1805034), RANKL (rs1054016) and OPG (rs1032128) by real-time PCR. The frequency of genotypes and alleles was assessed using chi-squared test or Fisher's exact test and odds ratio. Interactions were also tested using multifactor dimensionality reduction (α = 5 %). ResultsIn the polymorphism rs1800629 in TNF-α, carrying at least one A risk allele significantly decreased the risk to develop PAP (OR=0.47; 95 %CI: 0.28–0.79; p=0.004). For the polymorphism rs1054016 in RANKL carrying both T risk alleles significantly decreased the risk to develop PAP (OR=0.47; 95 %CI: 0.24–0.92; p=0.027). None of the other polymorphisms evaluated were associated with PAP (p>0.05). A strong interaction was observed among rs1800629, rs1061622 and rs1054016. ConclusionsGenetic polymorphisms rs1800629 (TNF-α) and rs1054016 (RANKL) had a strong interaction and were associated with a lower risk to develop PAP.

Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant.

Background: High variability in the age at cancer diagnosis in Lynch syndrome (LS) patients is widely observed, even among relatives with the same germline pathogenic variant (PV) in the mismatch repair (MMR) genes. Genetic polymorphisms and lifestyle factors are thought to contribute to this variability. We investigated the influence of previously reported genetic polymorphisms on the age at cancer diagnosis in a homogenous LS cohort with a South African founder germline PV c.1528C>T in the MLH1 gene. Methods: A total of 359 LS variant heterozygotes (LSVH) from 60 different families were genotyped for specific genetic polymorphisms in GSTM1, GSTT1, CYP1A1, CYP17, PPP2R2B, KIF20A, TGFB1, XRCC5, TNF, BCL2, CHFR, CDC25C, ATM, TTC28, CDC25C, HFE, and hTERT genes using Multiplex Polymerase Chain Reaction and MassArray methods. Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards gamma shared frailty models adjusted for sex were used to estimate the association between age at cancer diagnosis and polymorphism genotypes. A p-value < 0.05 after correcting for multiple testing using the Benjamini-Hochberg method was considered significant at a 95% confidence interval. Results: We identified three genotypes in the cell-cycle regulation, DNA repair, and xenobiotic-metabolism genes significantly associated with age at cancer diagnosis in this cohort. The CYP1A1 rs4646903 risk (GG) and CDC25C rs3734166 polymorphic (GA+AA) genotypes were significantly associated with an increased risk of a younger age at cancer diagnosis (Adj HR: 2.03 [1.01-4.08], p = 0.034 and Adj HR: 1.53 [1.09-2.14], p = 0.015, respectively). LSVH who were heterozygous for the XRCC5 rs1051685 SNP showed significant protection against younger age at cancer diagnosis (Adj HR: 0.69 [CI, 0.48-0.99], p = 0.043). The risk of a younger age at any cancer diagnosis was significantly high in LS carriers of one to two risk genotypes (Adj HR: 1.49 [CI: 1.06-2.09], corrected p = 0.030), while having one to two protective genotypes significantly reduced the risk of developing any cancer and CRC at a younger age (Adj HR: 0.52 [CI: 0.37-0.73], and Adj HR: 0.51 [CI: 0.36-0.74], both corrected p < 0.001). Conclusions: Polymorphism genotypes in the cell-cycle regulation, DNA repair, and xenobiotic metabolizing genes may influence the age at cancer diagnosis in a homogenous LS cohort with a South African founder germline PV c.1528C>T in the MLH1 gene.

The association between polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 AND TNF< genes with susceptibility and severity of SARS-COV-2 infection

The association between polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 AND TNF< genes with susceptibility and severity of SARS-COV-2 infection

Association between rs1799724 of TNF- α gene and early onset preeclampsia in Chinese: A pilot study

ObjectiveTo investigate the association between polymorphisms of TNF- α (rs1799724, rs1800629), VEGF (rs3025039) and VEGFR1 (rs 722503) and early onset preeclampsia (EOPE) in Chinese. MethodsA total of 132 EOPE patients from January 2016 to December 2018 at the Second Hospital of Tianjin Medical University were selected as the EOPE group, and 156 normal pregnant patients as the Control group. In both groups, 5 ml of peripheral venous blood was obtained after admission. The characteristics of genotype and allele distribution at the four SNPs in the study subjects were examined by matrix-assisted laser desorption ionization time-of-flight mass spectrometric genotyping. ResultsThe genotype frequency distribution and allele frequency distribution of rs1799724 were significantly different between the EOPE group and the Control group (P = 0.002，P = 0.003). The T allele was statistically associated with the development of EOPE under a dominant genetic model (P = 0.001). The genotype and allele frequency distributions of rs1800629, rs3025039, and rs 722503 did not differ significantly between the EOPE group and the Control group (P > 0.05). There was no linkage disequilibrium among rs1799724, rs1800629 and rs3025039 loci, the corresponding haploid cannot be formed. ConclusionsThe rs1799724 of TNF- α gene is a genetic susceptibility locus for EOPE and may be a potential predictors of preeclampsia.

Genetic markers associated with adverse reactions of radioiodine therapy in thyroid cancer patients.

Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes ofDNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients. The study included 181 patients (37 men, 144 women; median age 56 [41; 66.3] years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. NFKB1, ATM, ATG16L2, ATG10, TGFB1, and TNF polymorphisms were determined by allele-specific realtime-PCR. The frequency of adverse reactions was the following: gastrointestinal symptoms- 57.9 %, local symptoms- 65.8 %, cerebral symptoms- 46.8 %, fatigue- 54.4 %; signs of sialoadenitis six months after radioiodine therapy- 25.2 %. TT genotype carriers of ATG10 rs1864183 had higher frequency of gastrointestinal symptoms (vs. CC+CT), the CC genotype carriers of ATG10 rs10514231 had significantly more frequent cerebral symptoms (vs. CT+TT), as well as AA genotype carriers of TGFB1 rs1800469 (vs. AG+GG). CC genotype of ATG10 rs10514231 increased the incidence of radioiodine-induced fatigue, whereas GA genotype of the ATM rs11212570 had a protective role against fatigue. TGFB1 rs1800469 was associated with signs of sialoadenitis six months after radioiodine therapy. Genetic factors may contribute to the occurrence of adverse reactions of radioiodine therapy in thyroid cancer patients.

Genetic markers associated with adverse reactions of radioiodine therapy in thyroid cancer patients.

Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes ofDNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients. The study included 181 patients (37 men, 144 women; median age 56 [41; 66.3] years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. NFKB1, ATM, ATG16L2, ATG10, TGFB1, and TNF polymorphisms were determined by allele-specific realtime-PCR. The frequency of adverse reactions was the following: gastrointestinal symptoms- 57.9 %, local symptoms- 65.8 %, cerebral symptoms- 46.8 %, fatigue- 54.4 %; signs of sialoadenitis six months after radioiodine therapy- 25.2 %. TT genotype carriers of ATG10 rs1864183 had higher frequency of gastrointestinal symptoms (vs. CC+CT), the CC genotype carriers of ATG10 rs10514231 had significantly more frequent cerebral symptoms (vs. CT+TT), as well as AA genotype carriers of TGFB1 rs1800469 (vs. AG+GG). CC genotype of ATG10 rs10514231 increased the incidence of radioiodine-induced fatigue, whereas GA genotype of the ATM rs11212570 had a protective role against fatigue. TGFB1 rs1800469 was associated with signs of sialoadenitis six months after radioiodine therapy. Genetic factors may contribute to the occurrence of adverse reactions of radioiodine therapy in thyroid cancer patients.

Investigation of TNF-&amp;alpha; and DC-SIGN promoter polymorphisms in patients with dengue fever in Lahore city of Pakistan

&lt;p&gt;&lt;strong&gt;Background and Objective:&lt;/strong&gt; Dengue fever (DF) has been a major health concern globally. Pakistan is also combating this infection for the last decade. Cytokine genes play an important role in DF pathogenesis. This study aimed to analyze dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and tumor necrosis factor &amp;alpha; (TNF-&amp;alpha;) genes promoter polymorphisms in DF patients.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A total of 140 (n = 140) dDF patients were recruited for study at the Department of Human Genetics and Molecular Biology of University of Health Sciences, Lahore, Pakistan over a period of 3 years. Simple DF was noted in 105 patients (75%) while 35 (25%) showed bleeding complications. All patients were found positive for dengue non-structural protein or dengue IgM. All patients were tested for two polymorphisms in TNF-&amp;alpha; (-238G/A, and -308G/A) and one polymorphism in DC-SIGN (-336G/A) using restriction fragment length polymorphism technique. A single nucleotide polymorphism stats program was used for statistical analysis.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Susceptibility to develop dengue infection in the presence of -336G allele odds ratio (OR = 27.95, p = &amp;lt;0.0001) and GG genotype (OR = 183.77, p = &amp;lt;0.0001) was found to be significantly associated in this study. Presence of a combination of alleles -336G/-238A/-308A was noted in 59.4% of DF cases and 7.6% healthy controls, a difference with statistical significance (OR = 31.46, p = &amp;lt;0.0001). Moreover, prevalence of DF symptoms showed a trend higher in G-carriers versus non-G-carriers of DC-SIGN -336 polymorphism.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; This work suggests a potential association of DC-SIGN -336 polymorphism with susceptibility to develop symptomatic dengue illness. However, no potential association was found between TNF-&amp;alpha; promoter polymorphisms and dengue infection in this study.&lt;/p&gt;

TNF and MMP1 gene polymorphisms and their association with clinical aspects of colorectal cancer

Aim. To evaluate associations of polymorphic variants of some genes with such clinical aspects of colorectal cancer as gender, age of manifestation of the disease, localization of the tumor, the stage of the process at the time of manifestation. Materials and methods. Polymorphic variants of TNF and MMP1 genes were evaluated in 178 patients. The main group consisted of 110 patients with colorectal cancer, the control group consisted of 68 healthy volunteers. Genotyping was performed by DNA isolation from leukocytes of venous blood of the subjects followed by PCR with electrophoretic detection of the result. Description and comparison of differences in the frequencies of qualitative traits in independent groups was performed using Pearson’s χ2 criterion. Odds ratios (OR, 95% confidence interval) were also calculated for polymorphism variants that showed a correlation relationship. Differences at p<0.05 were considered statistically significant in the analysis. Results. Polymorphic variants of TNF gene (G308A) showed association with colorectal cancer in men and women, age of manifestation 50-59 and 60-69, 70 and older, localization of tumor in rectum and colon, I-III stages of tumor process. Polymorphic variants of MMP1 gene (1607 1G/2G) are associated with the development of colorectal cancer in women, age of manifestation 60-69 years old, colorectal cancer stage I-III. Conclusion. The results obtained suggest that not only risk factors influence the development of colorectal cancer, but also the human genetic status itself contributes to the development of tumors of these localizations.

Polymorphisms in some proinflammatory genes (TNFα and β, IL-1β, IL-6, ADAM17) in severe chronic venous disease.

Chronic venous disease (CVD) is a common disorder of lower extremities. The study was scheduled to investigate the relationship between polymorphisms in major proinflammatory genes TNF α (-238 A/G; -308 A/G), TNF β (NcoI), IL-1β (+3953 T/C); IL-6 (-174 G/C; -596 G/C) and ADAM17 (3'TACE) and CVD risk. Genotype-phenotype study was calculated to test possible association between examined genotypes and phenotypes of CVD. Finally, 150 CVD patients and 227 control subjects were enrolled to the study. Genotypes in proinflammatory gene polymorphisms were identified from isolated DNA by PCR method and restriction analysis. Significant differences in genotype distribution/allelic frequencies in TNF β gene, IL-1 β gene and in ADAM17 gene polymorphisms were found between CVD women and control ones. In the genotype-phenotype study, identified genotypes were associated with arterial hypertension (ADAM17, IL-6-men), ischaemic heart disease (TNF α and β genes), diabetes mellitus (ADAM17-women, TNF β-men), age of CVD onset (TNF α and IL-6), ulceration (ADAM17), duration of ulceration (ADAM17), ulceration recurrence (ADAM17-women), home care necessity (TNF α), varices surgery (TNF α), erysipelas development (ADAM17-men) and tumour development (TNF α). Studying of these polymorphisms associations can help us better identify patients at higher risk of developing severe CVD.

The rs17713054 and rs1800629 polymorphisms of genes LZTFL1 and TNF are associated with COVID-19 severity

Geneticheskiye i negeneticheskiye faktory otvetstvenny za vysokuyu mezhlichnostnuyu variabel'nost' otveta na SARS-CoV-2. Khotya geneticheskiye polimorfizmy byli identifitsirovany kak faktory riska tyazhelogo techeniya COVID-19, oni okazalis' nedostatochno izuchennymi v rossiyskoy populyatsii. Tsel'yu dannogo issledovaniya bylo vyyavit' geneticheskiye determinanty, svyazannyye s nagruzkoy na techeniye COVID-19 na vyborke patsiyentov iz Rossiyskoy Federatsii. Provedena otsenka svyazi geneticheskikh polimorfizmov rs17713054 v gene LZTFL1 i rs1800629 v gene TNF (faktor nekroza opukholi) s tyazhest'yu COVID-19. Byli issledovany DNK 713 patsiyentov (324 muzhchiny i 389) vozrastom 18‒95 let s COVID-19, protekavshey s raznoy massoy. Identifitsirovany rs1800629 TNF (OR = 1,5; p = 0,02) i rs17713054 LZTFL1 (OR = 1,60; p = 0,0043) kak faktory riska tyazhelogo proyavleniya. Polimorfizmy TNF rs1800629 i LZTFL1 rs17713054 yavlyayutsya potentsial'no prediktivnymi i prediktivnymi biomarkerami. Pokazana sil'naya zavisimost' rs17713054 G &gt; A s nagruzkoy na grafik. Polucheniye dannykh o razvitii zabolevaniy v rezul'tate razvitiya testov-sistem prognozirovaniya riska vozniknoveniya virusnykh zabolevaniy respiratornogo trakta.

Study of the effect of RS1800629 TNF polymorphism on the course of age-related macular degeneration through the prism of ANTI-VEGF therapy

Annotation. Age-related macular degeneration (AMD) includes pathological changes in the deep layers of the retina, macula, and surrounding blood vessels, leading to loss of central vision. The wet form of nosology is the leading cause of irreversible blindness in developed countries among people over 60, where more than 30 million people suffer from the disease. The number of patients in the United States is expected to increase from 9.1 million in 2010 to 17.8 million in 2050. New therapeutic strategies and the development of new practical methods for identifying patients at high risk of treatment resistance are needed to reduce the prevalence of the disease. That is why the aim of the study was to shed light on the role of the rs1800629 polymorphism of the TNF gene as one of the prognostic factors in the effectiveness of treatment of the wet form of AMD. The study group consisted of 162 people diagnosed with a wet form of pathology, while the comparison group consisted of 105 people without a history of ophthalmic pathology. Optical coherence tomography of certain areas of the eye, including the retina, was used to confirm or rule out the diagnosis. To detect the polymorphism status of the TNF gene, the real-time polymerase chain reaction method was used on the BioRad CFX 96 thermocycler-amplifier, using “Litekh” (RF) reagent kits. Statistical processing of the results was performed by determining the Hardy-Weinberg equilibrium, Student’s and Wilcoxon’s criteria, logistic regression using OR values and 95% CI, and by subtracting RR and χ². The study found that the frequency of genotype distribution with mutant allele A was predominant among patients in the study group, and the G allele was determined predominantly in the control group and was associated with better results of anti-VEGF therapy. The results of OCT confirmed this information, because among carriers of genotypes GG and GA (p&lt;0.05) visual acuity improved even after the first injection of the drug in most areas, while among carriers of homozygous genotype AA was not sufficient probability of biological effects, efficiency in the presence of this genotype was reduced (p&lt;0,05). The results of treatment were most representative in the areas of OCT 4, OCT 8 and macula (OCT 3) – among carriers of allele A in the OCT 4 zone, the chance of resistance to treatment was 3.1 times (OR=3.1; 95% SI 1,686 - 5.7) higher than in carriers of the G allele, and in the zone of OCT 8 in patients from the study group the risk of ineffectiveness of therapy was 2.81 times (OR=2.81; 95% CI 1.56 - 5.059) higher than in the corresponding zone of the G allele carriers. This suggests a lack of clinical efficacy in individuals carrying the mutant A allele, and the need to identify the status of polymorphisms for prognostic assessment of treatment efficacy.

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll-like receptors dictates pathophysiology of COVID-19 disease.

Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease‐19 (COVID‐19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID‐19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID‐19 or severe acute respiratory syndrome coronavirus‐2 (SARS‐COV‐2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID‐19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll‐like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID‐19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID‐19 disease severity. Understanding host immune gene variations associated with the SARS‐COV‐2 infection opens insights to control the pathophysiology of emerging viral infections.

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes.

IntroductionKidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved over the past two decades. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for kidney transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene (TNF) polymorphisms on kidney graft survival after transplantation.MethodsWe performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function and death-censored kidney allograft survival in 1271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.ResultsThe G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of immediate graft loss (odds ratio: 2.05; 95%-CI: 1.06–3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05–2.19, P = 0.028).DiscussionIn conclusion, kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.

Involvement of polymorphisms of TNF, CRP and SAA1 genes in the predisposition to the development of ankylosing spondylitis and its clinical manifestations

Objective. To study the involvement of the rs1800629 G/A polymorphisms of the TNF-α gene, rs1205C/T of the CRP gene, and rs12218T/C of the SAA1 gene in the predisposition to ankylosing spondylitis (AS) and their role in the formation of clinical phenotypes of AS.Materials and methods. 122 patients with AS were included in the study. All patients had a diagnosis of AS based on the modified New York criteria. The presence of the HLA-B27 antigen was detected in 109 (89.3%) patients, the presence of peripheral arthritis – in 71 (58.2%), enthesitis – in 92 (75.4%), coxitis – in 82 (67.2%) patients. All patients had a high degree of activity with an average BASDAI index of 5.6±1.2. The control group consisted of 142 healthy blood donors. Polymorphisms were studied using allele-specific real-time polymerase chain reaction (RT-PCR).Results. Significant differences were found in the frequencies of genotypes and alleles of the -308G/A polymorphism of the TNF gene and the frequencies of alleles of the rs12218 T/C polymorphism of the SAA1 gene between patients and the control group (p=0.01, p=0.01 and p=0.03 respectively). Logistic regression analysis showed that the presence of at least one -308A allele in the patient’s genotype reduced the risk of developing AS by 4.4 times compared with the GG genotype (p=0.006). In carriers of the GA genotype, the probability of a predisposition to the development of enthesitis was 2.2 times lower than in carriers of the GG genotype (p=0.01). The relationship between the rs1205 polymorphism of the CRP gene and the predisposition to peripheral arthritis has been established. Carriage of the rs1205T allele doubled the susceptibility to arthritis compared with the rs1205C allele (p=0.013). Carriage of at least one rs12218C allele of the SAA1 gene doubled the susceptibility to AS (p=0.018).Conclusion. The data obtained confirm the involvement of polymorphisms rs1800629 of the TNF gene, rs1205 of the CRP gene, and rs12218 of the SAA1 gene in the predisposition to AS. TNF gene polymorphism is associated with the formation of the clinical phenotype of enthesitis, and CRP gene polymorphism is associated with a predisposition to peripheral arthritis.

Genetic polymorphisms in TNF-α as a potential biomarker for oral health-related quality of life in children.

This cross-sectional study aimed to assess if genetic polymorphisms in TNF- α are associated with a negative impact on Oral Health-Related Quality of Life (OHRQoL) in children with dental caries. A total of 307 pairs of parents/caregivers and children aged two to five years were selected. The children were clinically evaluated and classified according to caries experience and severity of active caries. The Brazilian Portuguese version of the Early Childhood Oral Health Impact Scale (ECOHIS) was used to assess OHRQoL. Genotyping analysis of genetic polymorphisms in TNF- α (rs1799724, rs1799964, and rs1800629) was performed using real-time polymerase chain reaction. In the recessive model, children with the CC genotype of TNF-α (rs1799964) had a significantly high chance of poor OHRQoL in the symptom domain (pain), in both the caries experience (p = 0.045) and the high-severity active caries phenotypes (p = 0.033) (Mann-Whitney U test). It was concluded that genetic polymorphisms in TNF-α are associated with OHRQoL related to the symptom domain (pain), suggesting that TNF-α could be used as a potential biomarker for OHRQoL. Understanding the genetic aspects associated with OHRQoL will allow the early identification of patients with OHRQoL disparities and provide personalized healthcare.

Cytokine gene polymorphisms of TNF, IFN-γ, and IL-12 as potential predictors in the onset of cervical disease in HR HPV-positive women with behavioral risk cofactors

Introduction/Objective. The aim of this study was to investigate the distribution of genotypes and alleles of proinflammatory cytokines TNF, IFN-?, and IL-12 and their effect on the development of a cervical illness and also to determine their associated influence with cofactors in HR HPV-positive women in Serbia. Methods. We have investigated 24 women and based on the cytological findings they were classified into four groups: PAP II, ASCUS, LSIL, and HSIL. Analysis of TNF, IL-12, and IFN-? polymorphisms was performed using the real-time PCR TaqMan method. Statistical analysis was performed using parametric and non-parametric tests and correlation and multiple regression analysis. Results. Significantly higher frequency of high production-related TNF AA genotype was observed in severe dysplasia. The correlation between TNF gene polymorphism and cervical findings were highly significant. There was a moderate, significant correlation between low production IFN-? AA genotype and earlier cervical infections. There was a significant correlation between the IL-12 polymorphism of the low production IL-12 AA genotype and cervical lesions. Conclusion. Results of this study show that HSIL is associated with significantly higher frequency of high production TNF AA genotype. It is known that polymorphisms of certain cytokine genes encoding proteins involved in Th1 and Th2 cellular responses may be associated with better or worse prognosis of cervical disease in women with persistent HR HPV infection. Therefore, they may be considered as biomarkers that may have a predictive role in the development of cervical cancer.

Frequency of hyperglycemia and polymorphism of TNF and TP53 genes in patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer

BACKGROUND: «The vicious circle» of associations of diabetes mellitus (DM) with pancreatic pathology, when pancreatic diseases can initiate DM, and type 2 DM — cause functional and organic pancreatic pathology, determines the search for possible associations. Some studies have established a relationship between TNF or TP53 polymorphisms with DM or with pancreatic diseases.AIMS: to determine and compare fasting plasma glucose and the frequency of hyperglycemia in patients with acute pancreatitis (APp), chronic pancreatitis (CPp), pancreatic cancer (PCp) depending on gender, etiology or stage of the disease, polymorphism -308G/A TNF gene in all patients, and polymorphism 72Arg/Pro gene TP53 in PCp..MATERIALS AND METHODS: At the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: frequency of hyperglycemia in APp, CPp, PCp, considering the polymorphism TNF and TP53 genes. RESULTS: The lowest age-standardized fasting plasma glucose (FPG) was found in CPp (6,2±0,2 mmol/l) than in APp (6,7±0,2 mmol/l, p=0,041). In PCp (6,6±0,2 mmol/l), the average levels of FPG did not differ substantially when compared with APp (p=0,749) or CPp (p=0,092). In APp, the norm of GP was detected less frequently (31,8%) than in CPp (54,6%, χ2 =6,3, p=0,012), and the frequency of the norm of GP in PCp (48,9%) did not differ with that in APp or CPp. The frequency of FPG≥6,1&lt;7,0 mmol/l did not differ in APp (20,5%), CPp (9,3%) or PCp (17,8%). The frequency of FGP≥7.0 mmol/l did not differ in APp CPp and PCp: 47,7, 36,1, 33,3%. Logistic regression analysis revealed a tendency for an increased chance of having stage 3–4 PC with FPG≥7,0 mmol/l (Exp (B)=3,205 95%CI 0,866–11,855, p=0,081) in PCp, but not in patients with pancreatic necrosis or “definite» СP.The frequencies of G/G (71,4, 74,7, 76,2%), G/A (26,2, 24,1, 23,8%) of TNF genotypes did not differ in APp, CPp or PCp, p&gt;0,05. In PCp genotypes Arg/Arg, Arg/Pro, Pro/Pro polymorphism gene 72Arg/Pro TP53 in 2,4, 35,7, 61,9% of cases. No associations of GP≥7,0 mmol/l with TNF polymorphism in APp, CPp, PCp and with TP53 polymorphism in PCp were obtained.CONCLUSIONS: The frequency of FGP≥7,0 mmol/l did not differ for various pancreatic disease and was not associated with the risk of pancreatic necrosis and “defined” CP. The -308G/A polymorphism TNF gene did not differ in APp, CPp or PCp and was not associated with impaired carbohydrate metabolism. The 72Arg/Pro polymorphism TP53 gene in PCp was not associated with impaired carbohydrate metabolism.

Tumor necrosis factor-α gene promoter −308 and −238 polymorphisms and its serum level in psoriasis

BackgroundPsoriasis is a chronic, immune-mediated, inflammatory skin disease affecting genetically predisposed individuals and requiring long-term treatment. The etiology of psoriasis is not fully understood. This article aimed to determine association between genetic polymorphisms in tumor necrosis factor-α (TNF -α) promoter −308 (rs1800629) and −238 (rs 361,525) and its serum level in psoriasis patients. MethodsThe study was conducted on 70 patients with psoriasis and 70 age and sex-matched, healthy individuals. All patients were subjected to history taking and complete medical examination. The polymorphisms of TNF -α promoter gene −308 (rs1800629) and −238 (rs 361,525) were detected by real time PCR and Serum levels of TNF -α were measured by ELISA technique. ResultsAG polymorphism and A allele of TNF-α −238 G/A (rs 361,525) were significantly more in patients than controls, whereas AG polymorphism and A allele of TNF-α −308 G/A (rs1800629) were significantly more in controls than patients. There were significant high levels of TNF-α in serum of patients in comparison to controls. ConclusionsThe AG polymorphism and A allele of TNF-α −238G/A (rs 361,525) may act as a risk factor for occurrence of psoriasis, whereas AG polymorphism and A allele of TNF-α −308G/A (rs1800629) may have protective role. There is pivotal role of TNF-α as a pro-inflammatory mediator in pathogenesis of psoriasis.

Lack of association between TNF polymorphism and ankylosing spondylitis susceptibility in HLA-B27-positive population: a meta-analysis.

Human leukocyte antigen (HLA)-B27 plays a crucial role in the pathogenesis of AS. TNF polymorphisms have been reported to be associated with AS susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether TNF polymorphism is associated with AS susceptibility in HLA-27-positive population. Our search was done in the Pubmed, Embase, and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in HLA-B27-positive population. Ten studies from 8 articles were included in this meta-analysis. In the population of HLA-B27-positive patients and random healthy controls, there were statistical significance in the evaluation of association between the minor allele of TNF-238, -308, -857, -1031 and -863 and AS susceptibility, respectively. In the population of HLA-B27-positive patients and HLA-B27-positive healthy controls, there were no statistical differences in the comparison of minor allele of with their respective major allele in the fixed model. There was no association of the TNF polymorphisms with AS in the HLA-B27-positive AS group and HLA-B27-positive control group. Polymorphisms of TNF-238, -308, -857, -1031, -863 were associated with AS susceptibility in the HLA-B27-positive AS patients and random control population. Other gene SNPs except TNF may play an important role in AS susceptibility in HLA-B27-positive population.

IL17F: A Possible Risk Marker for Spondyloarthritis in HLA-B*27 Negative Brazilian Patients.

HLA-B*27 is an important marker for spondyloarthritis (SpA), however, many SpA patients are HLA-B*27 negative. Thus, the aim of this study was to investigate the influence of IL17, TNF and VDR gene polymorphisms in SpA patients who were HLA-B*27 negative. This case-control study was conducted in 158 patients [102 patients with ankylosing spondylitis (AS) and 56 with psoriatic arthritis (PsA)] and 184 controls. HLA-B*27 genotyping was performed using PCR-SSP and IL17A (rs2275913), IL17F (rs763780), TNF-308 (rs1800629), TNF-238 (rs361525), FokI C>T (rs2228570), TaqI C>T (rs731236), ApaI A>C (rs7975232), and BsmI C>T (rs1544410) using PCR-RFLP. Statistical analyses were performed by Chi-square and logistic regression using OpenEpi and SNPStats software. The IL17F C allele frequency was higher in patients with SpA, AS and PsA compared to controls. The IL17F T/C genotype frequency was higher in SpA patients in an overdominant inheritance model and when men and women were separately analyzed. IL17A_IL17F AC haplotype was significantly associated to the risk for SpA patients. As for VDR, the ApaI a/a was a potential risk factor for SpA in men. In conclusion, IL17F C variant contributed to the risk of SpA in Brazilian patients who were HLA-B*27 negative and could be a potential marker for SpA.