TNF-α Polymorphisms Research Articles

Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants.

Background The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. Methods A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. Results No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067–4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316–18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010–14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605–11.023, P = 0.004). Conclusions Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

Genetic polymorphisms of TNF-α, IL-6, and IL-10 in female elderly patients with chronic temporomandibular disorder pain.

To verify the association of the TNF-α, IL-6, and IL-10 polymorphisms with chronic temporomandibular disorder pain development in female elderly patients. Participants were evaluated according to Diagnostic Criteria for Temporomandibular Disorders. The genomic DNA was extracted from blood according to the Salting Out method followed by a quantification using the NanoDrop spectrophotometer. The -308G/A TNF-α polymorphism analysis was performed by the polymerase chain reaction-restriction fragmentlength polymorphism technique, the determination of -174G/C IL-6 polymorphism was performed by polymerase chain reaction, and the evaluation of the -1082A/G IL-10 polymorphism was carried out by polymerase chain reaction- allele-specificamplification. Data were analyzed using the BioEstat 5.3 software. The -308G/A TNF-α polymorphism showed a significant difference when genotypes of cases with chronic temporomandibular disorder pain and controls were compared (p=.025). There was a lack of association regarding the -174G/C IL-6 polymorphism (p=.286) however, a positive association between the -1082A/G IL-10 polymorphism with chronic temporomandibular disorder was observed (p=.020). The analyzed data of elderly subjects support the possible involvement of the GA genotype of the -308G/A TNF-α and the AA genotype of the -1082A/G IL-10 polymorphisms in the pathogenesis of chronic temporomandibular disorder pain.

TNF-α (G308A) Polymorphism and Vascular Parkinson Complicated with Pulmonary Infection.

To analyse relationship between tumour necrosis factor-α (TNF-α) (G308A) polymorphism and Vascular Parkinson (VP) complicated with pulmonary infection. Analytical study. Zhuji people's Hospital, China, from February 2017 to April 2021. Eighty five patients with VP complicated with pulmonary infection were included in the observation group. Eighty five patients with VP were included in the comparison group. Genotypic analysis of TNF-α (G308A) and serum TNF-α were detected. TNF-α (G308A) polymorphism in both the observation group and control group conformed to the genetic balance rule by the Hardy-Weinberg test. The frequency of each gene satisfied the genetic balance (p=0.175, and p=0.184, respectively). Genotype distribution and alleles of TNF-α (G308A) between the observation group and the control group were different (both p <0.001). Compared with control group, serum TNF-α level in the observation group was higher (p <0.001). In the observation group, serum TNF-α level in cases with GA+AA genotype (carrying A allele) was higher than that in cases with GG genotype (non A allele) (p <0.001). TNF-α (G308A) polymorphism is associated with VP complicated with pulmonary infection. VP Patients with TNF-α (G308A) AA genotype and an allele may have a high risk of pulmonary infection. Tumor necrosis factor-α (TNF-α), Polymorphism, Vascular Parkinson (VP), Pulmonary infection.

The Role of the IL-10 (−819C/T), TNFA (−308G/A) and ENOS (−786T/C) Polymorphisms of Impulsive and Aggressive Personality Traits in Cocaine/Crack Users

Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (−819C/T), TNFA (−308G/A) and ENOS (−786T/C) polymorphisms were determined by Real-Time PCR. In addition, the relationship between these polymorphisms and Impulsivity and Aggression was determined. We found that the physical aggressiveness sub score was negatively correlated with the C allele of −819C/T polymorphism of the IL-10 (b = −0.14; p = 0.04). The T allele of the SNP −786T/C of the ENOS gene positively predicts traits of physical aggressiveness (b = 0.14; p = 0.04). The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of −308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (−819C/T), TNFA (−308G/A) and ENOS (−786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.

Relationship of Bactericidal Permeability Increasing Protein (BPI) Polymorphysm rs1341023, rs5743507, Tumor Necrosis Factor Alpha (TNF-α) rs361525, rs1800629 with Neonatal Sepsis

Background: Neonatal sepsis is a problem in the field of child health because the incidence is increasing every year and often ends in death. This study aimed to investigate the relationship between TNF-α and BPI gene polymorphisms with neonatal sepsis.&#x0D; Methods: PCR and sequencing examinations were performed on 60 DNA samples consisting of 30 samples of neonatal sepsis and 30 samples of non-neoptic sepsis. Furthermore, data in the form of DNA mutation tables were statistically processed by univariate, bivariate, and multivariate analysis. It is considered meaningful if p&lt;0.05.&#x0D; Result: The results showed that BPI rs1341023, rs5743507 and TNF-α rs361525, rs1800629 only BPI rs1341023 and TNF-α rs1800629 were mutated. Of the two genes, only TNF-α rs1800629 had a significant association with neonatal sepsis (p&lt;0.05).&#x0D; Conclusion: This study proved that the TNF-α rs1800629 mutation was the most important polymorphism in the occurrence of neonatal sepsis (p&lt;0.05).&#x0D; Keywords: BPI, TNF-α, Neonatal, Polymorphism, Sepsis

Genetic Association between TNFA Polymorphisms (rs1799964 and rs361525) and Susceptibility to Cancer in Systemic Sclerosis.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (p = 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (p = 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (p = 0.03) and GG carriers (p = 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.

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.

Assessment of gastric caused by Helicobacter pylori and pathologic elements correlation with -511 IL1-β and -308 TNF-α polymorphisms in gastritis patients

Helicobacter pylori (H.pylori) is the main reason for gastric disorders including gastric lymphoma, ulcer disease, gastric carcinoma (GC), and chronic atrophic gastritis. H.pylori has two more significant virulence factors named cagA and vacA. Some host cytokines polymorphisms (Interleukin (IL-1) and tumor necrosis factor (TNF-α)) may contribute to H. pylori-related diseases. In the present study, we investigated the association of H. pylori gastritis and its pathogenic genes as well as the association of IL-1β and TNF-α polymorphisms in patients with gastritis. We collected gastric biopsy samples from patients with gastritis. After extracting DNA from biopsy specimens infected with H. pylori, cagA + and vacA + were detected by the polymerase chain reaction (PCR). To genotyping TNF-α polymorphism at position −308 and IL-1β polymorphism at position −511, PCR-based restriction fragment length polymorphism analysis was performed. Our study indicated that IL-1β-511 polymorphism, unlike TNF-α-308 polymorphism (P = 0.030), did not show a significant relationship between patients infected with H. pylori (p = 0.219). Also, our results indicated that alleles C and T of polymorphism of IL-1β-511 and alleles G of TNFα-308 were not significantly correlated with cagA status among patients infected with H. pylori (p = 0.793, p = 0.674, p = 0.179, respectively) unlike allele A of TNFα −308 (p = 0.016).

Evidence of Association between MTRR and TNF-α Gene Polymorphisms and Oral Health-Related Quality of Life in Children with Anterior Open Bite.

To assess the impact of AOB on OHRQoL in children and to evaluate whether MTR (rs1805087), MTRR (rs1801394), TGFβ1 (rs1800469) and TNF-α (rs1799964, rs1799724 and rs1800629) genes are potential biomarkers for OHRQoL in children with AOB. A cross-sectional study was performed with 173 children aged between 2-6 years. The Brazilian version of Early Childhood Oral Health Impact Scale (ECOHIS) was applied. Genetic polymorphisms were analyzed using real-time PCR. Mann-Whitney U-test and Chi-square were used. The overall mean ECOHIS scores were 5.49 (SD= 5.72) and 3.45 (SD = 4.49) (p < 0.01) in the AOB and control groups, respectively. Children with the CC genotype of TNF-α (rs1799724) had a significantly higher psychological QoL level. The MTRR AA genotype group showed a lower QoL level in the child subscale (p = 0.006), function (p = 0.017), and psychological (p = 0.006) domains. There was no significant difference between OHRQoL and the genetic polymorphisms in MTR and TGFβ1. Genetic polymorphisms in TNF-α and MTRR are associated with the impact on the OHRQoL in children with AOB.

On assessing risks of developing and progressing non-alcoholic fatty liver disease using TNF-α, IL6, and VEGF factors and polymorphisms of their genes

Our research aim was to develop a system for calculating risks of development and progression of non-alcoholic fatty liver disease (NAFLD). The system would be based on interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) and TNF-α gene polymorphism in the region -308G/A (rs1800629), IL-6 in the region –174G/C (rs1800795), and VEGFA in the region –634G/C (rs2010963). We examined 52 patients with NAFLD and 65 healthy donors. The examination involved estimating levels of cytokines TNF-α, IL-6 and VEGF in blood serum. We also studied the polymorphism of the TNF-α genes in the -308G/A region, IL-6 in the -174G/C region, and VEGFA in the -634G/C region. Women aged from 32 to 54 years prevailed among patients with NAFLD (67 %). We established in this research that concentrations of the pro-inflammatory cytokines TNF-α, IL-6 and the level of VEGF in the blood serum were significantly higher in patients with NAFLD than in the reference group (p = 0.03; p = 0.00003 and р = 0.001 accordingly). This confirms an occurring inflammatory syndrome and endothelial dysfunction that are typical for this pathology. Patients with NAFLD tended to have the AA genotype of the TNF-α -308G/A gene (rs1800629) significantly more frequently than healthy donors (р = 0.04). Homozygote CC and allele C of the VEGFA gene (G-634C) in the position rs2010963 were significantly more often detected in the test group (patients with NAFLD) than in the reference one (p = 0.02 and p = 0.01 respectively). We didn’t detect any statistically significant differences in the IL-6 gene polymorphism in the -174G/C (rs1800795) region in the analyzed groups. TNF-α -308G/A gene polymorphism correlated with activating production of TNF-α and IL-6 cytokines (Ki = 0.588; p = 0.043 and Ki = 0.597; p = 0.04, respectively), which can lead to developing immune-inflammatory syndrome in its carriers. When determining genetic profiles, we established that 51 % donors had low risks of NAFLD development whereas the risk was high for 75 % of patients with the disease. The risk of developing NASP is associated with carrying the AA genotype of the TNF-α -308G/A gene and the CC genotype of the VEGFA -634G/C gene. Assessment of a genetic profile using these markers provides an opportunity to assess risks of developing NAFLD in healthy people and to predict its progression in patients with the disease.

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.

Effect of tumor necrosis factor alpha (TNF-α) -308 and -1031 gene polymorphisms on periodontitis among Saudi subjects

ObjectivesPeriodontitis is an infectious disorder that leads to irreversible loss of the surrounding attachment and bone destruction. Genetic polymorphism of cytokines has been suggested to play a role in periodontitis. This case-control study aimed to investigate the relationship between periodontitis and two single nucleotide polymorphisms (SNPs): rs1800629 (-308 G/A) and rs1799964 (-1031 T/C), in the TNF-α gene promoter area. Materials and methodsPeripheral blood was used to prepare genomic DNA from 60 subjects with stage II to stage III periodontitis, as along with 65 control subjects. Polymerase chain reaction and restriction endonuclease digestion were used to genotype TNF-α SNPs. ResultsThe distribution of both genotypes and alleles of TNF-α (-308 G/A) polymorphism did not vary between periodontitis subjects and the controls (P > 0.05). However, the CT genotype and C allele of the TNF-α (-1031 T/C) polymorphism were observed more frequently in the periodontitis subjects than in the controls, while the TT genotype and the T allele were more predominant in the control subjects than in the periodontitis patients (OR: 3.149; 95% CI: 1.494–6.639; P = 0.002 and OR: 2.933; 95% CI: 1.413–6.090; P = 0.003, sequentially). ConclusionThe TNF-α (-308 G/A) polymorphism potentially has no correlation with periodontitis susceptibility, whereas the TNF-α (-1031) CT genotype and C allele might be related to periodontitis among Saudi subjects.

IL-10 (-819C/T), TNFA (-30G/A) and ENOS (-786T/C) Polymorphisms Modulating the Outcome Related to Mental Disorders in Crack Addicted Users.

Cocaine/crack use affects immune system molecules and development of mental disorders has been identified. To investigate the relationship of polymorphisms in the TNFA (-308G/A), IL-10 (-819C/T) and ENOS (-786T/C) genes with mental disorders in cocaine and crack users. A case-control study was carried out, which included 107 cocaine and crack users and 115 controls who never used healthy cocaine and crack. The SNPs in the TNFA (-308G/A), IL-10 (-819C/T) and ENOS (-786T/C) genes were genotyped by real time PCR. As for the individuals included in this study, the average age of 31.4 years (± 8.59). We identified that the G/A genotype to TNFA (-308) (OR = 0.24; p = 0.03) and the A allele (OR = 0.30; p = 0.03) were associated with reduced risk for dysthymic disorder. The T allele of the IL-10 (-819) polymorphism was associated with decreased risk of developing panic disorder (OR = 0.44; p = 0.01), while the C allele was correlated with an increased risk for alcohol dependence (OR = 1.97; p = 0.04), alcohol abuse (OR = 1.81; p = 0.04) and psychotic syndrome (OR = 2.23; p = 0.01). C/C genotype was correlated with increased chances of developing current psychotic syndrome (OR = 4.23; p = 0.01). Our results suggest that genetic polymorphisms promote susceptibility or promote protection for clinical phenotypes of psychiatric comorbidities in cocaine and crack users and be considered as good prognostic markers.

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.

The Genetic Polymorphism of TNF-α Associated with the Anti-TNF-α Therapy Used for COVID-19 Patients – Another Possible Approach

Objective: This work aimed of to review the implications of anti-TNF-α therapy in COVID-19 patients associated with the genetic polymorphism (TNF-α polymorphisms in the region-308) of this pertinent cytokine Methodology: Electronic searches were carried out on PUBMED Central, BVS/BIREME, Web of Science and The Cochrane Library with the aid of key-words. Results: Twenty-six articles were collected. Anti-TNF-α therapy was interpreted and evaluated. Conclusions: Although scarce information is available in the current literature, anti- TNF-α therapy seems to be a viable clinical approach for hospitalized COVID-19 patients who do not need oxygen supply. The genetic polymorphisms, although relevant, may be useful for further researched to assess the clinical response in different research groups.

A Systematic Review and Meta-Analysis on Multiple Cytokine Gene Polymorphisms in the Pathogenesis of Periodontitis.

AimPeriodontitis is an inflammatory disease that destroys both soft and hard periodontal tissues. However, a complex periodontal cytokine network remains unclear. This systematic review explored multiple cytokine gene polymorphisms in the pathogenesis of periodontitis.Material and MethodsA systematic search was performed using the databases from previous publications, which indicated the association between cytokine polymorphisms and periodontitis pathogenesis. Meta-analysis was conducted using fixed or randomized models to calculate the significance of multiple cytokine polymorphisms. A total of 147 articles were analyzed with polymorphisms in 12 interleukins [Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4 and IL-13), Th17 (IL-1α, IL-1β, IL-6, and IL-17), and Treg cytokines (IL-10 and TGF-β)]. Doi plot was used to probe the occurrence of publication bias.ResultsThe polymorphisms of IL-2 and TNF-α of Th1 cytokine family may be associated with the pathogenesis or the prevention of periodontitis risk, while the polymorphism of IFN-γ is not related to periodontitis risk. The polymorphisms for IL-4 and IL-13 of Th2 cytokine family are not found to be associated with the pathogenesis of periodontitis. For the polymorphisms of the members of Th17 cytokine family, different IL-1α polymorphisms may have inverse actions in the pathogenesis of periodontitis. IL-1β is a noteworthy cytokine biomarker in periodontitis development and progression. IL-6 may have a protective function in the inflammatory responses of periodontitis, and IL-17 has a weak relationship the inflammatory responses. The polymorphisms for the members of Treg cell cytokines may have a protective function against periodontitis risk. LFK indexes show the major asymmetry due to publication bias.ConclusionIL-1β is a notable cytokine biomarker in periodontitis risk. Treg cytokines favor an anti-inflammatory and protective environment. Further data are needed to confirm the present conclusion due to publication bias.

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.

TNF-α levels and presence of SNP-308G/A of TNF-α gene in temporomandibular disorder patients.

ABSTRACTIntroduction: Temporomandibular disorder (TMD) refers to a group of conditions that compromise the harmonious movement and function of the temporomandibular joint, masticatory muscles, and associated structures. The etiopathogenesis of TMD is multifactorial but not well-understood, with the role of genetic factors still being unclear. Objective: This review aims to summarize the results of studies that evaluated TNF-α levels and the -308G/A TNF-α polymorphism in TMD patients. This study emphasizes the importance of a more selective treatment involving TNF-α inhibitors that can potentially reduce inflammation and pain, and improve quality of life.Methods: The MEDLINE/PubMed database, Cochrane Library, and Web of Science database were searched for case-control studies published until September 2020 that compared levels of TNF-α or presence of its -308G/A polymorphism in TMD patients and healthy individuals. Results: Six case-control studies were identified with a total of 398 TMD patients, aged between 12 and 78 years. The control group consisted of 149 subjects, aged between 18 and 47 years. The occurrence of TMD was predominant in females. Majority of studies found high TNF-α levels in TMD patients, compared to the control group. One of these studies found a positive correlation between the GA genotype and the development of TMD.Conclusion: Majority of the TMD patients showed elevated TNF-α levels, and a possible explanation for this could be the presence of the -308G/A polymorphism.

The role of cytokine gene single nucleotide polymorphism in the development of recurrent acute otitis media

The study aimed at examining the role of single nucleotide polymorphism (SNP) of cytokine genes in the development of recurrent acute otitis media (AOM) among children. Single nucleotide polymorphism of IFN-, IL-6, IL-10, TNF-α, and TGF-β1, were analyzed by the polymerase chain reaction with sequence-specific primers (PCR-SSP) in 82 children with recurrent AOM and compared with a similar control group. There was a significant higher incidence of IL-10 polymorphisms (loci -592, -819 and -1082) in children with recurrent AOM (P=0.0137, 0.0137 and 0.0072, respectively). However, there was no significant difference in the distribution of other cytokine genotypes between the two study groups. Among the 5 studied cytokine genes, only IL-10 loci showed significant correlation to the development of recurrent AOM.

Genetic polymorphism of cytokines IL-1β, IL-4 and TNF-α as a factor modifying the impact of childhood adversity on schizophrenia symptoms

Based on the hypothesis that activation of the immune system is one of the mechanisms of influence of early environmental factors on the onset and course of schizophrenia, we investigated the effects of the interaction of childhood adversity and IL-1β rs16944, IL-4 rs2243250 and TNF-α rs1800629 polymorphisms on schizophrenia symptomatology. The sample consisted of 546 patients with schizophrenia spectrum disorders. The presence of childhood adversity was determined based on the analysis of medical records and a questionnaire completed by the patient. We used the 5-factor model of the Positive and Negative Syndrome Scale (PANSS) with the nested two-factor negative syndrome model. After adjusting for multiple comparisons, a significant effect of the interaction of childhood adversity and TNF-α on the cognitive/disorganization factor was found, with a difference between genotypes in the group without childhood adversity (pFDR <0.018; η2p=0.03). A significant effect of the interaction of childhood adversity and genotype on the cognitive disorganization syndrome was established (F=5.87; p=0.003; η2p=0.03). Stereotyped thinking and avolition on PANSS had the highest correlations with cognitive disorganization factor (ro=0.84 and ro=0.82, respectively) and the highest significance of differences depending on the interaction of genotype and childhood adversity (Kruskal-Wallis test, H=12.28, p=0.006 and H=12.79, p=0.005, respectively). Childhood adversity modifies the relationship between the pathogenesis of schizophrenia and the TNF-α promoter polymorphism rs1800629, which is also an enhancer of another 60 genes located in the major histocompatibility complex.