TNF-α Single Nucleotide Polymorphisms Research Articles

Implications of cytokine genes polymorphisms in Jordanian patients with obsessive compulsive disorder

BackgroundObsessive–compulsive disorder (OCD) is a common and often highly debilitating chronic neuropsychiatric condition. There is substantial evidence that immune system and genetic changes are involved in OCD pathogenesis. Only a few studies have been encountered in the literature in this field. We aimed at providing experimental evidence for single nucleotide polymorphisms (SNPs) in candidate cytokine genes for the etiology of OCD.MethodsA total of 52 OCD patients and 54 healthy controls were randomly recruited from the Jordanian population. Age ranged between 16 and 55 years (35.5 ± 13.72 and 33.5 ± 10.48 years) for patients and controls, respectively. Five polymorphic positions in four interleukin genes (IL-1β; rs16944 and rs1143634, IL-6; rs1800795, IL-10; rs1800896 and rs1800795) were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. The tumor necrosis factor-α (TNF-α) SNP (rs1800629) DNA was sequenced by the Sanger method. The obtained data were analyzed using the GraphPad Prism method.ResultsThere were no statistically significant differences between the alleles and genotypes in opposite groups. However, there was a positive association between the incidence of the studied SNP cytokine genes in OCD patients and non-OCD individuals. The alleles of two SNPs (IL-1β + 3954 C > T and TNF-α-308 G > A) were more predominant and more positively correlated with a higher risk in OCD women. In contrast, the link between the gender and the occurrence of the mutant alleles of the other four SNPs IL-1β (− 511 C > T); IL-6 (− 174 G > C); IL-10 (− 1082 A > G); and IL-10 (− 819 C > T was more robust in the males OCD patients than the corresponding females.ConclusionThe observed differences between the alleles in different groups may be due to an association in the tested samples rather than a true association. But, the possibility of a critical effect still exists. One might want to explore this further by repeating the study with a larger sample size.

TLR4 and TNF-α single nucleotide polymorphisms in patients with brucellosis: Association with infection complications

To investigate associations of the carriage of single nucleotide polymorphisms (SNPs) of proteins involved in the immune response of patients with brucellosis. A case control study of patients with brucellosis upon WHO criteria. Blood genomic analysis was performed by RFLP- PCR for the detection of SNPs: i) at promoters -376 G > A (rs1800750); -308 G > A (rs 1,800,629); -238 G > A (rs361525) of the TNF gene, ii) at -896 A > G Asp299Gly (rs4986790) and -1196 C > T Thr399Ile (rs4986791) positions of the TLR-4 gene. Logistic regression analysis of factors related to brucellar spondylodiscitis was performed. Patients with brucellosis (n = 105) were male (n = 67, 63.8 %); mean age (SD): 49.51(18.31); spondylodiscitis (n = 30), sacral osteomyelitis (n = 21). Carriage of the minor frequency A alleles at -238 of the promoter region of TNF was greater in patients than in controls (11.4% vs 2.6 %, p < 0.001). In a stepwise regression model including host variables and TNF-238 G A-1 genotype, only the last one was associated with brucellar spondylodiscitis [OR 2.91 (CI95 % 1.02-8.31), p = 0.047]. In our cohort, the association of one TNF SNP of patients with brucellosis, in particular spondylodiscitis, might be prognostic whereas further investigation of the exact role in the host immune response is required.

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

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

The role of TNF-α and il-6 SNP in polycystic ovary syndrome susceptibility.

Aim: To shed the light on the impact of TNF-α 1031 T/C (rs-1800629) and IL-6 174 G/C (rs1800795) polymorphism with disease susceptibility and development. Materials and Methods: A case-control study has been established based on 50 women with confirmed diagnosed polycystic ovarian syndrome, and 50 healthy controls. Allele specific PCR have been done in order to study SNP of TNF-alpha and IL-6 in both groups. Result: The findings of the present investigation indicated that there was a signif i cant dif f erence in the frequency distribution of TNF-alpha 1031 T/C SNP according to genotype between patients and controls group p = 0.02. In addition, there is a high significant difference in the frequencies of distribution of alleles (T/C) between patients and control group p = 0.001. There was a signif i cant dif f erence in the frequency distribution of IL-6 174 G/C between patients and controls group p = 0.026. In addition, there is a signif i cant dif f erence in the frequencies of distribution of participants according to allele (G/C) between patients and control group p = 0.047. Genotype GC was significantly lower in patients' group and genotype GG was high significant in patients' group in comparison with a control group and the differences were significant, p = 0.024 and 0.006, respectively. Conclusions: The present study concluded that IL-6 174 G/C, (rs:1800795) single nucleotide polymorphism (SNP) and TNF-alpha 1031 T/C (rs-1800629) were associated with PCOS susceptibility, and GG genotype in IL-6 and C allele in TNF are considered as risk factor.

IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.

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

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

Plasma Cytokine Levels and Cytokine Genetic Polymorphisms in Patients with Metastatic Breast Cancer Receiving High-Dose Chemotherapy

Differences in the baseline levels of serum cytokines or in single-nucleotide polymorphisms (SNPs) in cytokine genes may be useful to predict outcomes for patients being treated for metastatic breast cancer. We have measured the plasma levels and characterized individual SNPs for IL-1RA, IL-1β, IL-2, IL-6 and TNFα in 130 patients with metastatic breast cancer treated with high-dose chemotherapy. Patients were treated with high-dose cyclophosphamide (Group 1, 74 patients) or high-dose paclitaxel-containing regimens (Group 2, 56 patients). A high plasma level of IL-1RA and a SNP in the IL-1RA gene indicated a better prognosis for patients in Group 1 (but not Group 2). However, the level of plasma IL-1RA did not correlate with the SNP genotype. A high plasma level of IL-6 or TNFα indicated a poorer outcome for patients in Group 1 although the SNP genotypes for the IL-6 and TNFα SNPs were not associated with differences in outcome. The plasma levels of IL-1β and IL-2 and the genotype of the IL-1β SNPs did not indicate differences in outcome. Although, individually, plasma levels of cytokine or “risk” SNP genotypes may not indicate outcome, in combination there was an increased trend to predict outcome for patients treated with high-dose cyclophosphamide but not high-dose paclitaxel. These results suggest that the immune cytokines may be useful as prognostic biomarkers in the treatment of patients with metastatic breast cancer treated with different types of chemotherapy.

Association of Tumor Necrosis Factor-α 308A/G Gene Polymorphism with Obesity among a Population of Southwestern Nigeria

Obesity often results from interplay of genetics, nutrition and lifestyle. A polymorphic variant of the Tumor Necrosis Factor-α (TNF- α) promoter region (308G/A) is associated with increased production of TNF- α protein, which could lead to fat accumulation implicated in the development of obesity and cardiovascular disease. This study investigated the association of TNF-α 308G/A polymorphism with obesity among a population residing in Southwestern Nigeria. Two hundred (200) obese and 197 age and sex matched non-obese subjects were enrolled. Blood pressure, weight, height, waist and hip circumferences were measured. Estimation of fasting blood sugar level, DNA extraction from whole blood and genotyping of single nucleotide polymorphisms of TNF-α 308G/A were done using standard laboratory procedures. Data were analyzed and p-value &lt; 0.05 was considered significant. Mean body weight and BMI were significantly increased in the obese group (81.92±1.00 kg, 33.01±0.25kg/m2) compared with controls (72.03±1.01 kg, 22.06±0.22kg/m2). Waist and hip circumferences were increased among obese subjects (p&lt;0.05). Occurrence of A allele was higher (85.3%) than G allele (68.5%) among participants. Frequency of AA genotype was 51% (OR: 8.137, CI: 3.882 - 17.060, P=0.01) in obese subject and 11.34% in the non-obese, wild GG genotype was lower in obese (6%) than non-obese individuals (23.71%). Heterozygous AG occurred more in non-obese (64%) than obese (43%) subjects. Homozygous AA variant of TNF-α 308 is strongly associated with occurrence of obesity among the studied population. There was no association between GG variant of TNF-α -308 and obesity

Tumor Necrosis Factor-α, CD1A and CD1E Genetic Polymorphisms in Guillain-Barré Syndrome: A Study from India.

Guillain-Barré Syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of peripheral nerves and roots. The pathogenesis is essentially an aberrant post-infectious immune response in a genetically susceptible host milieu. Single nucleotide polymorphisms (SNP) in genes encoding the inflammatory mediators like TNF-α, CD1A and CD1E can influence their expression and level and the susceptibility and clinical course of disease in GBS. We tried to study the susceptibility of single nucleotide polymorphisms of TNF-α and CD1 genes in Guillain-Barré Syndrome in Indian population and determine the association in terms of genotype, allele and haplotype distribution along with individual subtype, severity and clinical outcome. In this case-control study, we investigated the single nucleotide polymorphism pattern in the promoter region of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E genes using real-time polymerase chain reaction in 75 GBS patients and analysed in comparison with 75 age and sex-matched healthy controls. The findings revealed that the allelic distribution of TNF-α (-308 G/A) *A allele was associated with GBS (P value 0.04, Odds Ratio 2.03, 95% Confidence Interval 1.01-4.07). There was no association found with genotype, haplotype combination and other allele distribution for GBS in the study. CD1A and CD1E SNPs did not reveal any susceptibility for GBS. The subtype analysis did not reveal any statistical significance, except for CD1A *G allele with AMAN subtype (P value 0.026). The haplotypic combinations and mutant allele of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E were significantly associated with severe GBS in the study. However, there was no association of any SNP for mortality and survival of GBS in the study. TNF-α (-308 G/A)*A allele might confer genetic susceptibility for GBS in Indian population. CD1 genetic polymorphism could not be considered for susceptibility to GBS. TNF-α and CD1 genetic polymorphism did not affect mortality in GBS.

Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis.

Human diseases are generally influenced by SNPs (single nucleotide polymorphisms). The mutations in amino acid residues generated by deleterious SNPs contribute to the structural and functional diversity of the encoded protein. Tumor necrosis factor-α (TNF-α), Glucocorticoid receptor gene (NR3C1), and Cytochrome P450 3A5 (CYP3A5) play a key role in glucocorticoid resistance susceptibility in humans. Possible causative mutations could be used as therapeutic targets and diagnostic markers for glucocorticoid resistance. This study evaluated the missense SNPs of TNF-α, NR3C1, and CYP3A5 to predict their impact on amino acid changes, protein interaction, and functional stability. The protein sequence of dbSNP was obtained and used online in silico method to screen deleterious mutants for the in silico analysis. In the coding regions of TNF-α, NR3C1, and CYP3A5, 14 deleterious mutations were discovered. The protein functional and stability changes in the amino acid between native and mutant energy were identified by analyzing the changes in the hydrogen bonding of these mutants from native, which were all measured using Swiss PDB and PyMOL. F446S and R439K had the highest root-mean-square deviation (RMSD) values among the 14 deleterious mutants. Additionally, the conserved region of amino acid protein interaction was analyzed. This study could aid in the discovery of new detrimental mutations in TNF-α, NR3C1, and CYP3A5, as well as the development of long-term therapy for corticosteroid resistance in several inflammatory diseases. However, more research into the deleterious mutations of the TNF-α, NR3C1, and CYP3A5 genes is needed to determine their role in corticosteroid resistance.

The TNF-α -308G/A Gene Polymorphism and Serum TNF-α Levels in Women with Preeclampsia

Objective: Worldwide, preeclampsia (PE) is a multifactorial disorder reported in 2–5% of pregnancies, which increases mortality during pregnancy. In general, 10–15% of maternal deaths are directly related to PE and eclampsia. One of the susceptibility genes for PE is tumor necrosis factor-α (TNF-α) expressed by most immune cells. TNF-α is a protein involved in various biological processes, including proliferation and apoptosis, as well as the expression of inflammatory genes. The goal of this study was to investigate the role of TNF-α single nucleotide polymorphism (SNP) -308G/A (rs1800629) and their relationship with TNF-α in PE patients.&#x0D; Materials and methods: The SNP was genotyped in 90 cases and 90 controls. Whole blood was collected from women with PE and normal pregnancy in EDTA containing tubes, and DNA extraction was performed from their blood lymphocytes according to a standard phenol-chloroform procedure. Then, DNA was genotyped by real-time PCR and the polymorphism was detected by TaqMan assay. Serum levels of TNF-α protein were measured by enzyme-linked immunosorbent (ELISA) assay.&#x0D; Results: TNF-α levels in women with PE were significantly higher than in healthy ones (p&lt;0.001). We did not observe any correlation between allelic outbreak (p=0.3) and TNF-α-308G/A polymorphism (p=0.7) with the incidence of PE.&#x0D; Conclusion: Although TNF-α-308G/A gene polymorphism does not appear to affect susceptibility to PE, an increased level of serum TNF-α can be used as a predictor for PE during pregnancy. We recommend that more research be conducted on possible factors related to the incidence of PE.&#x0D;

Association Study of TNF-α -308 G/A (rs1800629) and -863 C/A (rs1800630) Polymorphisms with Systemic Lupus Erythematosus in the Iranian Lor Population

Background: Systemic lupus erythematosus (SLE) is caused by a combination of environmental and genetic factors; studying the association between regulatory genes and this disease may determine the genetic causes of interfering with SLE. In different populations, studies have shown that the tumor necrosis factor α (TNF-α) gene (as a candidate gene) can contribute to the formation and progression of lupus disease. Objectives: This study aimed to indicate the possible association between the increased rate of SLE hazard and 2 single-nucleotide polymorphisms (SNPs) of rs1800629 and rs1800630 genetic polymorphisms in the TNF-α promoter gene in the Lor population. Methods: According to the American College of Rheumatology (ACR) criteria, 120 unrelated SLE patients and 120 healthy controls with no family or personal history of autoimmune diseases were selected. DNA was genotyped for the TNF-α promoter (-308 G/A and -863 C/A) by the tetra-primer amplification-refractory mutation system (tetra-primer ARMS)–polymerase chain reaction (PCR) method. Results: The frequency difference between allele A (mutant allele) and allele C (normal allele) at position -863 of the TNF-α promoter gene (odds ratio [OR] = 3.426; 95% CI, 1.985 - 5.914) was notably higher in SLE patients than in control subjects. Also, a significant relation was obtained among the rs1800830 AA genotype and increased risk of SLE (OR = 4.489; 95% CI, 2.464 - 8.177; P &lt; 0.0001). Our results for rs1800629 at position -308 were not remarkably different. Conclusions: We found a significant correlation between allelic and genotype frequencies between rs1800830 (-863 C/A) TNF-α SNP and SLE in our study. However, no significant correlation was observed between the rs1800629 (-308 G/A) TNF-α promoter and the increase of SLE hazard in the Lor population. No remarkable association was obtained between TNF-α gene rs1800629 (-308 G/A) and rs1800630 (-863 C/A) SNPs and anti-double-stranded DNA (anti-dsDNA) or antinuclear antibody (ANA), which are some of the symptoms of SLE.

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

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

STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.

Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PIt0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer 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.

Genotype TNF-α(-308) and Silicosis on Factory Workers in Vietnam in 2020

The studFigy aims to determine the TNF-α single-nucleotide polymorphism TNF-α (-308) andassess the association of TNF-a(-308) SNP with the risk of silicosis among workers directly exposed tosilica dust in Vietnam. A study was undertaken among 78 cases with silicosis and 103 controls withoutsilicosis in Vietnam. Blood samples were collected for genomic DNA extraction from each subject. Thephenotyping of TNF-α(-308) was performed using polymerase chain reaction‐based restriction fragmentlength polymorphism (PCR‐RFLP) and dye termination sequencing. Results: The average exposure timeof the case group was slightly higher than that of the control group (12.46 ± 6.732 years vs. 12.09 ± 7.854years). The majority of genotypes in both silicosis and non-silicosis was GG. When analyzing theconcentration of TNF-α in the study participants' blood, it is shown that the average concentration of TNF-α in the case group was higher than that in the control group. The genotype AG in the case group was1.368 times higher than that in the control group. The percentage of all A alleles in the case group withsilicosis was 1.342 times higher than the control group without the disease, similar to previous studies.Conclusion: The majority of genotypes in both groups was GG. The average concentration of TNF-α inblood, genotype AG, and the percentage of all A alleles in the case group was higher than that in thecontrol group.

Association analysis of genetic variants in the ghrelin and tumor necrosis factor α genes and the risk for non-Hodgkin's lymphoma in Kuwaitis.

BACKGROUND: Non-Hodgkin’s lymphoma (NHL) is the most common hematological malignancy in the world. Many etiologic factors have been implicated in the risk of developing NHL, including genetic susceptibility and obesity. Single-nucleotide polymorphisms (SNPs) in Ghrelin (GHRL), an anti-inflammatory hormone, and tumor necrosis factor (TNF-), an inflammatory cytokine, have been independently associated with the risk for obesity and NHL.OBJECTIVE: To investigate the association between SNPs in GHRL and TNF- and the risk for NHL and obesity in Kuwaitis.METHODS: We recruited 154 Kuwaiti NHL patients and 217 controls. Genotyping was performed for rs1629816 (GHRL promoter region), rs35684 (GHRL 3’ untranslated region), and rs1800629 (TNF- promoter region). Logistic regression analysis was performed to assess the association of the investigated SNPs with NHL and the relationship between the selected SNPs with BMI in each group separately.RESULTS: We show that rs1629816 GG was associated with an increased risk for NHL in our sample ( 0.0003, OR 1.82; CI: 1.31–2.54). None of the investigated SNPs were associated with obesity, nor was obesity found to be associated with the risk for NHL.CONCLUSIONS: Our study demonstrates an association between rs1629816, a SNP in the GHRL regulatory region, and NHL in Kuwaitis.

Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease.

Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single‐nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.

Functional study of TNF-α as a promoter of polymorphisms in psoriasis.

TNF-α is an important mediator in the pathogenesis of psoriasis and polymorphisms influence its transcription and could be implicated in psoriasis risk and modify certain aspects of disease, such as age at onset of psoriasis vulgaris and disease severity. Six TNF-α single nucleotide polymorphisms (SNPs) in promoter region has been identified and studied but with discordant results. The aim of this study was to evaluate whether the polymorphisms in TNF-α (-238 [rs361525], -308 [rs1800629], -857 [rs1799724], -1031 [rs1799964]) are associated with severity, itch, early onset or response to drug therapy in psoriasis in Caucasian Italian patients. Fifty-eight psoriasis patients from Turin PSOCARE, 23 with psoriasis vulgaris and 35 with psoriatic arthritis were studied. Ready-to-use master mix for allelic discrimination of rs1800629, rs361525 and rs1799964 respectively. Our data showed a significant association between the -857(G) variant and both VAS-itch (P=0.03) and VAS-pain index (P=0.006), OR=0.2 (0.04-0.98) and OR=0.12 (0.02-0.59). No significant association between the genotypes or alleles of TNF-α SNPs has been observed with other clinic-pathologic parameters or etanercept response. Our data suggest that -857 CC genotype could be involved in pain and itch severity in psoriasis patients.

Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882).

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).