TNF-alpha Polymorphisms Research Articles

TNF-alfa Gene Polymorphism Associations with Multiple Sclerosis.

Background:TNF-α has a dual role in multiple sclerosis (MS), contributing to both protective and harmful effects. It activates immune cells, promotes the formation of inflammatory lesions in the central nervous system, and stimulates the production of other pro-inflammatory cytokines and chemokines, leading to myelin destruction and neuronal damage. Our research focused on investigating the relationship between TNF-alpha (rs1800630, rs1800629, and rs361525) gene polymorphisms and MS. Methods: 250 healthy controls and 250 multiple sclerosis (MS) patients were included in the study. DNA was extracted from leucocytes from peripheral venous blood by salt precipitation. Single nucleotide polymorphisms (SNPs) were tested using RT-PCR. Statistical analysis of the data was performed using IBM SPSS Statistics 29.0 data analysis software. Results: The analysis revealed that the rs361525 AG genotype was significantly less frequent in the MS group compared to the control group (4.0% vs. 7.2%, p = 0.042). Sex-specific analysis showed a significant difference in genotype distribution (GG, AG, AA) among males between the MS group and the control group (97.7%, 0%, 2.3% vs. 90.6%, 9.4%, 0%, p = 0.005). For the rs1800629 polymorphism, significant results were also found. In subjects younger than 39 years, the A allele was significantly less frequent in the MS group than in the control group (8.6% vs. 15.0%, p = 0.030). The most robust model indicated that the AA genotype reduced the odds of MS by approximately 2 fold compared to the AG + GG genotype (p = 0.044), and each A allele reduced the odds of MS by approximately 2 fold (p = 0.028). The rs1800630 A allele was significantly more common in males in the MS group than in the control group (21.0% vs. 12.9%, p = 0.046). Conclusions: In conclusion, our study identifies significant associations between TNF-alpha gene variants and MS. Specifically, the rs631525 AG genotype was less common in the MS group, with notable sex-specific differences observed. The rs1800629 A allele was statistically significantly less frequent in the MS group than in the control group, and the AA genotype reduced the odds of MS occurrence by ~2 fold compared with the AG + GG genotypes. Additionally, each A allele of rs1800629 was linked to a 2-fold decreased odds of MS occurrence. In males, the rs1800630 A allele was more frequent in the MS group. These findings highlight the relevance of TNF-alpha genetic variations in MS susceptibility, suggesting potential avenues for further research and therapeutic exploration.

Evaluation of the association between TNF-α-1031 T/C polymorphism with oral lichen planus disease

BackgroundOral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between − 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population.MethodSaliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software.ResultsThe findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01–2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity.ConclusionsThese findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease.

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

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

Association of Interleukin-6 and Tumor Necrosis Factor-alpha Gene Polymorphisms with Gnetic Susceptibility of Psoriatic Arthritis in Kuwaiti Arab Patients

Background: Psoriatic arthritis (PsA) is an inflammatory arthritic disease in which joint inflammation occurs with psoriasis. It results from a complex interplay between genetic, immunological and environmental factors. In PsA, the activation of T cells is considered as a crucial step in the disease process. The T-lymphocytes affect the proliferation of epidermal skin cells and result in abnormal differentiation. Altered cytokine networks have been shown to play a central role in the pathogenesis of PsA. Psoriasis is characterized by Th-1 type cytokine pattern in which there is a marked variation in the secretion of interleukin-6 (IL6), interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha). This study investigated the association of IL6, IL13 and TNF-alpha gene polymorphisms with genetic susceptibility of PsA in Kuwaiti patients. Methods: The genotypes of IL6 gene (-174G/C; rs1800795), IL13 gene (R130Q; rs20541) and TNF-alpha gene (-308A/G’ rs1800629) polymorphisms were detected in 113 Kuwaiti PsA patients and were compared to that in 104 healthy controls. The PsA patients were diagnosed on the basis of the presence of inflammatory arthritis with psoriasis with no rheumatoid factor in the serum. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and were confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G’ rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti PsA patients and controls. However, the frequency of IL13 gene (R130Q; rs20541) polymorphism did not show a significant difference between Kuwaiti PsA patients and the controls. Conclusion: Our data show an association of two cytokine gene polymorphisms in IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G’ rs1800629) with PsA in Kuwaiti patients highlighting their significant contribution to genetic susceptibility of this chronic disease possibly along with other factors.

0118 Association between TNF-α G308A Polymorphism (rs1800629) and Insomnia Vulnerability in Fertile Age Women with Primary Dysmenorrhea

Abstract Introduction Higher tumor necrosis factor-alpha (TNF-α) gene expression has been revealed in the peripheral blood monocytes across the menstrual cycle in patients with primary dysmenorrhea (PDM) than in the unaffected control. Sleep quality is affected by environmental factors, endocrine function abnormalities and genetic factors. The aim of this study was to evaluate the effect of TNF-α G308A polymorphism (rs1800629) on the self-reported sleep, health, menstrual pain severity as well as peri-ovulatory serum TNF-α level in women with and without PDM. Methods Sleep, psychological and physiological characteristics and menstrual pain severity were collected with questionnaires and sleep/menstrual diary within a menstrual cycle from a cohort of 43 PDM women and 42 healthy controls (aged 20-30 years, right-handed, non-smoking and non-shift workers without psychiatric, sleep and neurological comorbidity). Chi-square tests were used to check if the genotype proportions of the investigated gene fitted the Hardy-Weinberg equilibrium (HWE) and to evaluate if the genotypic and allelic distribution is associated with PDM. Chi-square tests or analysis of variance were used to examine the effects of genotype, group and/or genotype x group interaction with the sleep, mind and the body health variables. Results Neither allele frequencies nor genotypes of TNF-α G-308A gene could serve as an independent risk factor of PDM in the Taiwanese population. Circulating serum TNF-α did not correspond with the -308 TNF-α promoter polymorphism, either, which might be due to a multifactorial control process. The TNF-α 308 A allele carriers (28.6%) which was less common than the G allele carriers (71.4%), showed lower Beck depression score, lower bodily pain and better physical health and higher subjective sleep quality. Furthermore, in G allele carriers, the PDM group showed higher insomnia severity and lower sleep duration than that of the control group. Conclusion Present results suggested that TNF-alpha polymorphism conferred no prediction to PDM risk and peri-ovulatory serum TNF-α level. However, our findings were evident that the A allele at the TNFα 308 locus, as compared to the more common G allele, was associated to better health and better sleep, with an indication of a genetic underpinning to their better resistance from the risk of PDM. Support (if any)

Estimating the role of single-nucleotide polymorphism (rs1800629)-308 G/A of TNF-alpha gene as genetic marker associated with angina pectoris in a sample of Iraqi patients

BackgroundAngina pectoris (AP) occurs when oxygen and other nutrients are insufficient to meet the metabolic needs of the heart muscle. Stable angina is the most common, while the unstable angina is less frequent. Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine plays a vital function in the immune response regulation. TNF gene cluster contains many polymorphisms; the most commonly investigated polymorphism is the rs1800629 SNP. This SNP, located at − 308 position with regard to the TNF promoter region, replaces guanine (G) with adenine (A), with the allelic types − 308 G/A, and has been linked to a variety of inflammatory condition and autoimmune diseases. The − 308 G/A SNP was investigated in AP and interconnected to the TNF level to figure out the responsibilities of TNF-alpha gene polymorphism in the pathogenesis of AP. MethodThe current work design as a case–control study that involves 300 participant divided to 200 patients evaluated as (stable angina n = 100 and unstable angina n = 100) compared with 100 apparently healthy control subjects. The serum level of TNF-alpha was assessed via enzyme-linked immunosorbent assay (ELISA)/sandwich method. The genotype and allele frequency distribution of TNF-alpha rs1800629 gene polymorphism were investigated by TaqMan probe of allelic discrimination method. ResultsThe levels of TNF-alpha were significantly higher in patients with stable and unstable angina pectoris in comparison with controls. The deviation from Hardy–Weinberg equilibrium (HWE) of TNF-alpha genotypes was obvious in control and unstable angina pectoris groups. Moreover, the significant differences between patients with AP and controls under the five genetic models consider the association between TNF-alpha (rs1800629) − 308 G/A and AP with OR > 1. However, data analysis of allelic and genotypic of (rs1800629) − 308 G/A revealed higher significantly differences of GG homozygous and GA heterozygous proportions between stable angina patients and control. The A allele was more represented as etiological allele, and G allele was represented as protective allele. The serum levels of TNF-alpha were significantly higher in subjects with genetically mutated AA genotypes than in subjects with wild GG genotypes in the study groups. ROC curve analysis found the best cutoff value of TNF-alpha level was 77.25 pg/ml. ConclusionAs the results, our data observed a linked of TNF-alpha (rs1800629) − 308 G/A genetic variant with angina pectoris patients, and the A allele has been linked to the production or expression of TNF-alpha serum level and represented an etiological factor of angina pectoris.

The Effect of TNF-Alpha Gene Polymorphisms At -376 G/A, -806 C/T, and -1031 T/C on The Likelihood of Becoming a Non-Responder to Etanercept in A Sample of Iraqi Rheumatoid Arthritis Patients

Tumor necrosis factor-alpha (TNF-α) antagonists’ therapy are expensive and has a non-responsive rate between 30% to 40% in rheumatoid arthritis patients. Genetic variation plays a vital role in the responsiveness to this type of therapy.The aim of this study is to investigate if the presence of genetic polymorphism in the TNF-α gene promoter region at locations -376 G/A (rs1800750), -806 C/T (rs4248158), and -1031 T/C (rs1799964) affects rheumatoid arthritis patient's tendency to be a non-responder to etanercept. Eighty RA patients on etanercept (ETN) for at least six months were recruited from the Rheumatology Unit at Baghdad Teaching Hospital. Based on The European League Against Rheumatism response (EULAR) criteria, patients were divided into two groups: responders and non-responders. After polymerase chain reaction amplification of their DNA, the amplified DNA was sequenced by Sanger method to determine the polymorphisms at the positions -376G/A, -806 C/T, and -1031T/C. The results of this study found that equally Phi correlation and binary logistic regression analysis revealed a non-significant association for all genotypes in the three polymorphic sites with the tendency for being non-responder. Moreover, there was no significant difference in TNF-α mean level or the change in disease activity score for 28 joints (DAS28) after six months of etanercept therapy between all genotypes for each polymorphic site. The present study concludes that there was no correlation between the polymorphisms in the TNF-α promoter region at -376G/A, -806 C/T, and -1031T/C with the tendency for being non-responder to ETN.

TNF-alpha gene polymorphism and its relation to vitamin D, calcium, alkaline phosphatase and ferritin status in Iraqi beta thalassemia patients

Introduction and Aim: Due to a lack of effective medications, beta-thalassemia is a serious issue in Iraq. Thus, the current investigation aimed to explore the relationship between TNF-alpha gene polymorphism G/A (rs 1800629), Vitamin D (Vit D), Calcium (Ca), alkaline phosphatase (ALP), and ferritin status in Iraqi beta thalassemia major and intermediate patients. Materials and Methods: Blood samples were collected from 46 patients suffering from thalassemia major (TM) plus 48 patients suffering from thalassemia intermediate (TI) and 48 of apparently healthy volunteers as control group aged 18-60 years, from Ibn Al-Baladi Hospital, Baghdad. Results: Studies for the distribution of TNF- alpha G/A (rs 1800629) genotype showed that among TM patients and TI patients, the prevalence of the mutant AA genotype (rs 1800629) was higher in TM patients, while in the control group, it was lower. Similarly, for the wild genotype (GG), the prevalence was highest in control group followed by T1 and TM patients. The frequency of A allele was high in TM patients, while the G allele frequency was more in the control group. Results also showed that the TNF- alpha genotype variations influenced Vitamin D, Calcium, ALP, and ferritin levels in TM and TI patients, wherein the patients with TNF-alpha mutant genotype (AA) were associated with highest levels of ferritin and ALP among all genotypes groups, while the patients of with TNF-alpha wild genotype (GG) were associated with high levels of Vitamin D and Calcium among all genotypes groups. Conclusion: Patients with at least one copy of (A) allele had a higher risk of TM and TI and there was an association between the heterogeneous (GA) and mutant (AA) genotypes, also presence of (A) allele with status differences of Vit D, Ca, ALP, and ferritin in Iraqi beta thalassemia major and intermediate patients.

Polymorphisms of TNF-alpha (− 308), IL-1beta (+ 3954) and IL1-Ra (VNTR) are associated to severe stage of endometriosis in Mexican women: a case control study

BackgroundEndometriosis is an estrogen-dependent and chronic inflammatory disease affecting up to 10% of women. It is the result of a combined interaction of genetic, epigenetic, environmental, lifestyle, reproductive and local inflammatory factors. In this study, we investigated whether single nucleotide polymorphisms (SNPs) mapping to TNF-alpha (TNF, rs1800629) and IL-1beta (IL1B, rs1143634) and variable number tandem repeat polymorphism mapping to IL1-Ra (IL1RN intron 2, rs2234663) genetic loci are associated with risk for endometriosis in a Mexican mestizo population.MethodsThis study included 183 women with confirmed endometriosis (ENDO) diagnosed after surgical laparoscopy and 186 women with satisfied parity and without endometriosis as controls (CTR). PCR/RFLP technique was used for genotyping SNPs (rs1800629 and rs1143634); PCR for genotyping rs2234663.ResultsWe found no statistical differences in age between groups nor among stages of endometriosis and the CTR group. We observed no difference in genotype and allele frequencies, nor carriage rate between groups in none of the three studied polymorphisms. The prevalence of TNF*2-allele heterozygotes (p = 0.025; OR 3.8), TNF*2-allele (p = 0.029; OR 3.4), IL1B*2-allele heterozygotes (p = 0.044; OR 2.69) and its carriage rate (p = 0.041; OR 2.64) in endometriosis stage IV was higher than the CTR group. Surprisingly, the carriage rate of IL1RN*2-allele (ENDO: p = 0.0004; OR 0.4; stage I: p = 0.002, OR 0.38; stage II: p = 0.002, OR 0.35; stage III: p = 0.003, OR 0.33), as well as the IL1RN*2-allele frequencies (ENDO: p = 0.0008, OR 0.55; I: p = 0.037, OR 0.60; II: p = 0.002, OR 0.41; III: p = 0.003, OR 0.38) were lower than the CTR group. Women with endometriosis stage IV (severe) had frequencies more alike to the CTR group in the IL1RN*2 allele frequency (31.2% vs. 27.2%) and carriage rate (37.5% vs. 41.9%).ConclusionAlthough these polymorphisms are not associated with the risk of endometriosis, Mexican mestizo women with severe stage of endometriosis have higher frequencies of TNF*2-, IL1B*2- and IL1RN*2-alleles, which may explain a possible correlation with disease severity rather than predisposition or risk.

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.

Analysis of Association between Interleukin-6 (&amp;lt;i&amp;gt;IL&amp;lt;/i&amp;gt;6), Interleukin-13 (&amp;lt;i&amp;gt;IL&amp;lt;/i&amp;gt;13) and Tumor Necrosis Factor-Alpha (&amp;lt;i&amp;gt;TNF-alpha&amp;lt;/i&amp;gt;) Gene Polymorphisms and Genetic Susceptibility of Rheumatoid Arthritis in Kuwaiti Arab

Background: Rheumatoid arthritis (RA) is a common autoimmune disease in which a combination of risk alleles from different susceptibility genes predisposes the patients to develop clinical symptoms following exposure to environmental factors. RA is a chronic and progressive disease characterized by synovial inflammation that results in destruction in the affected joints and severe problems in individual’s mobility. Several immune-related risk factors have been associated with RA, these include single nucleotide polymorphisms (SNPs) in cytokine genes. The impact of these cytokine gene polymorphisms is due to their association either with elevated serum levels and/or variations in their serum levels are associated with disease-onset and progression. The objective of this study was to investigate the role of Interleukin-6 (IL6), Interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in genetic susceptibility of RA in Kuwaiti patients. Methods: We have determined the genotypes of IL6 gene (-174G/C; rs1800795), IL13 gene (R130Q; rs20541) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms in 192 Kuwaiti patients with RA and compared it to that in 104 healthy controls. The diagnosis of RA was based on the American College of Rheumatology (ACR) classification criteria. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti RA patients and controls (P = 0.02 and 0.002 respectively). In contrast, the frequency of IL13 gene (R130Q; rs20541) polymorphism did not show a significant difference between Kuwaiti RA patients and controls. Conclusions: Our data showed an association of two cytokine gene polymorphisms (i.e. IL6 gene -174G/C; rs1800795 polymorphism, and TNF-alpha gene -308A/G, rs1800629 polymorphism) with RA in Kuwaiti patients highlighting their significant contribution in genetic susceptibility of this chronic disease possibly along with other factors.

Detection of TNF-α as a Cofactor in the Pathogenesis of Nasal Polypi

Abstract Background Nasal Polyposis (NP) is a complex multi-factorial disease; associated with several environmental, genetic and inflammatory factors. TNF-alpha is one of the major pro-inflammatory cytokines involved in NP pathogenesis. Some of the polymorphisms of this gene affect its expression. Aim of the Work To evaluate the polymorphism of TNF-alpha G/A308 gene and its association with nasal polyposis in Egypt. Patients and Methods In this case-control study, 25 patients with NP and 25 healthy individuals referred to Ain Shams University hospital were evaluated. After DNA extraction, RFLP-PCR was used to determine polymorphism. Chi-square test was used to compare the frequency distribution of genotype and alleles of TNFalpha gene with NP. The frequency of genotype G/G, A/A and G/A in the NP group was 8, 40 and 52%, and in the control group was 76, 1 and 5%, respectively. Results There was a statistically significant difference between genotype G/G in two groups (P = 0.0001). In addition, the frequency of allele A in patients and controls was 10 and 1%, respectively; and this difference was statistically significant (p = 0.0001). The findings of this study demonstrated that polymorphism in TNF-alpha gene might be a risk factor for NP in Egypt and the minor frequency of TNF-alpha G308A allele in the current study is slightly more than other major populations. However, more investigations with high number of population are necessary in future. Conclusion According to scientific evidence on TNF-α gene promoter G/A 308 polymorphism in Egypt, it seems that the pattern of genotypic distribution in all areas is the same. However, we found the greater amount of allele A in this study compared with the control group, and the occurrence of G/A genotype related to NP but for more valid results, a larger sample size is necessary. However on our results this polymorphism might be considered as a risk factor of susceptibility of NP in Egyptian people.

Meta-analysis on association between TNF-α and CCR5Δ32 gene polymorphisms and influenza A(H1N1)pdm09

Objective: To investigate the associations between TNF-α and CCR5Δ32 gene polymorphisms and influenza A(H1N1)pdm09. Methods: Studies in PubMed, Cochrane Library, OVID, EBSCO, Web of Science published before February 7, 2019 were retrieved comprehensively. Observational studies related to TNF-alpha and CCR5 gene polymorphisms and influenza A(H1N1) pdm09 were collected. A strict quality evaluation was carried out according to NOS scale. Meta-analysis was performed using software Revman 5.0 and Stata 11.0. Results: After screening, a total of 8 studies were included in this Meta-analysis. The results showed that TNF-α gene polymorphism rs361525 might be associated with the risk of influenza A(H1N1)pdm09 virus infection (A vs. G: OR=2.25, 95%CI: 1.09-4.65, P=0.03; AA vs. GG: OR=4.34, 95%CI: 1.65-11.41, P=0.003; AA vs. AG+GG: OR=4.38, 95%CI: 1.67-11.48, P=0.003), similar trend also found in rs1800750 (AA+AG vs. GG: OR=2.42, 95%CI: 1.24-4.71, P=0.01). The results of subgroup analysis indicated that A allele and AA+AG genotypes of rs361525 were risk factors for influenza A(H1N1) pdm09 virus infection in Caucasians. AA genotype was a risk factor for influenza A(H1N1) pdm09 virus infection in Mexican (P<0.05). There was no significant difference in the genetic polymorphism of CCR5 and the severity of influenza A (H1N1) pdm09 virus indection (P>0.05). Conclusion: People with allele A or genotype AA at rs361525, genotype AA+AG at rs1800750 of TNF-α gene might be more susceptible to influenza A(H1N1) pdm09.

Genetic Association between tumor necrosis factor (TNF-alpha and TNF-beta) gene polymorphisms and inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) is associated with chronic inflammation of the endothelial lining of the gut. Although, the exact aetiology is not completely understood, combined genetic and immunological factors appear to promote disease initiation and progression. Several studies associated the illness with single nucleotide polymorphism (SNP) on major immunological cytokines such as TNF-alpha and TNF-beta. Thus, the present study aims to investigate TNF-α and TNF-β genes polymorphisms in cases diagnosed with IBD. Subjects and methods:Genomic DNA isolation was performed on isolated buffy coat layers from peripheral blood of 75 individuals. Candidate SNP locations on TNF-α and TNF-β coding sequences were amplified by PCR and sequenced for SNP identification. Results:Genetic examination of TNF-α and TNF-β allele polymorphism revealed significant association with IBD prevalence and disease manifestation, (p=0.002) and (p<0.001) respectively. GA haplotype frequencies were higher in IBD patients when compared to healthy control, being 29(58%) in TNF-α, and 26(52%) in TNF-β of the studied alleles. Similarly, both GG and AA haplotypes of TNF-α showed a strong association with cases diagnosed with ulcerative colitis but not with Crohn’s disease (p=0.007). Additionally, none of the studied haplotypes of both cytokines showed any association with gender or age groups of the included individuals. ConclusioTNF-α (-308G/A) and TNF-β (+252A/G) sequence analysis revealed that cytokines heterogeneities are associated with IBD susceptibility. Early genetic screening for individuals with familial history could provide a better predictive value for IBD initiation and progression, that would essentially help in early diagnosis, management and prevention.

Tumor Necrosis Factor alpha 238 G/A polymorphism and its relation to severity and cardiovascular risk in psoriasis

Abstract Background Psoriasis is known as chronic immune-mediated inflammatory skin disease affecting about 3% of the world’s population. Cytokine gene polymorphism attracted considerable interest as they have been found to alter gene transcription thereby influencing inflammatory processes in response to various diseases. Subjects A total of 50 psoraitic patients and 50 controls were genotyped for TNF–α −238G/A polymorphism by using polymerase chain reaction. ECG and lipid profile were done to assess cardiovascular risk. Results Polymorphism of TNF–α −238 was not found to be associated with an increased risk for psoriasis (p value 0.98). There is significant difference between cases and controls as regard systolic and diastolic blood pressure . Conclusion Our findings suggest that there is no association between TNF alpha polymorphism and risk of psoriasis in Egyptian psoraitic patients.

Association between TNF-alpha polymorphism and the age of first suicide attempt in chronic patients with schizophrenia.

Patients with schizophrenia (SCZ) exhibit higher suicide rates than the general population. However, the molecular mechanism remains poorly understood. Tumor necrosis factor (TNF)-alpha polymorphisms have been repeatedly indicated to play a pathogenetic role in various mental disorders, but none of these studies focused on the susceptibility to suicidal behavior in SCZ. We recruited 1087 chronic inpatients with SCZ and 576 controls to assess the psychopathological symptoms of SCZ using the Positive and Negative Syndrome Scale scales. We selected 2 polymorphisms (-308G>A and -1031C>T) in the TNF-alpha gene and analyzed their associations with SCZ and suicide. Our results showed that TNF-alpha -308G>A and -1031C>T were not related to SCZ and suicide. However, we found that suicide attempters with the C allele carriers exhibited suicidal behaviors significantly later than those with TT genotype in the SCZ patients. The haplotype containing the T allele of the -1031 was significantly associated with the age of suicide initiation. Further logistic regression analysis showed that -1031C>T interacted with psychopathological symptoms and drinking, age of smoking, and related to the initiation age of suicide attempts. Our study demonstrated that the TNF-alpha variants may affect the age at which suicide attempts started among SCZ suicide attempters.

The role of TNF-alpha gene (-238G/A and -308G/A) polymorphisms in the etiology and pathogenesis of inflammatory bowel diseases in various ethnic groups

This literature review deals with specifics of the natural course of inflammatory bowel disease (IBD) in patients from various ethnic groups and -308G/A and -238G/A promoter polymorphisms in tumor necrosis factor-alpha (TNF-α) gene. The search in PubMed, Medline, Еlibrary.ru databases has led to identify in total 20 studies, including 2 meta-analyses, on the role of TNF-α-308G/A and -238G/A gene polymorphism in the etiology and pathophysiology of IBD. The TNF-α-308G/A polymorphism is associated with increased secretion of this proinflammatory cytokine, whereas the TNF-α-238G/A genotype is characterized by reduced TNF-α secretion. A number of studies have shown an association between TNF-α-308G/A gene polymorphism and severe course of IBD, requiring more active treatment of patients (cytostatics, corticosteroids, biological agents). Some investigators have found that the patients carriers of TNF-α-308G/A had a higher probability of surgical interventions. The association between TNF-α-308G/A and the phenotypic characteristics of IBD has been identified in studies performed in Europe, Asia, and Russia. The association of this polymorphism with the prevalence of ulcerative colitis has been proven in some studies, in particular, in the Asian population. Similar associations have been noted in few publications originating from Europe and North America, while some studies have found no links between TNF-α-308G/A, -238G/A, and the course of IBD. TNF-α-238G/A gene polymorphism has not shown any significance for the prevalence and course of ulcerative colitis and Crohn's disease. One can assume that the differences in the study results arising from one and the same geographical area are related to genetic heterogeneity of the study groups, phenotypic variances between the study subjects, as well as relatively small sample sizes. Currently, the search for genetic, biochemical and other prognostic criteria for IBD course is in progress. There are studies in progress to investigate the mechanisms of transformation of the genetic information into the particulars of ulcerative colitis and Crohn's disease manifestations, with consideration of ethnicity.

The Association between TNF-alpha Gene Polymorphisms and Endometriosis in An Iranian Population.

BackgroundTumor necrosis factor-alpha (TNF-α) is an important cytokine in acute inflammatory response to infective factors. Based on investigation in different populations, it is thought that this response increases in patients with endometrio- sis due to the presence of cytokines such as TNF-α. This study aimed to examine the association of four TNF-α polymor- phisms, namely -238G/A, -308G/A, -857C/T and -863C/A, with susceptibility to endometriosis in an Iranian population.Materials and MethodsWe recruited 150 women with endometriosis and 150 women without endometriosis in this case-control study and collected 4 ml of blood from all subjects. After DNA extraction, the polymorphisms were geno- typed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe allele frequency of TNF-α -863C/A in the case and control groups showed a significant difference [odds ratios (OR)=0.64, 95% confidence interval (CI)=0.41-0.99, P=0.047] but the result is not significant when Adjust- ing for multiple testing (P=0.188). No significant difference in the allele frequencies of -238G/A (OR=1.07, 95% CI=0.51-2.25, P=0.862), -308G/A (OR=0.79, 95% CI=0.43-1.45, P=0.438) and -857C/T (OR=1.03, 95% CI=0.66- 1.61, P=0.887) was observed. We adjusted all four polymorphism genotypes by age and body mass index (BMI), however, no significant difference was detected. There was an association between the case and control and BMI when adjusting by age (OR=1.082, 95% CI=1.009-1.162, P=0.028).ConclusionFor the first time the association of the four polymorphisms in the promoter region of the TNF-α gene with endometriosis has been conducted in women of Iranian origin. The present research reveals the -863 A allele may play a role in incidence of endometriosis among Iranian women. Development of endometriosis among those people with -863 A allele seems low. According to the results, the current study indicates that there might be a correlation between BMI and progression of endometriosis.

TNF-alpha G/A308 polymorphism association with nasal polyposis in North part of Iran.

Nasal Polyposis (NP) is a complex multi-factorial disease; associated with several environmental, genetic and inflammatory factors. TNF-alpha is one of the major pro-inflammatory cytokines involved in NP pathogenesis. Some of the polymorphisms of this gene affect its expression. Therefore, the aim of this study was to evaluate the polymorphism of TNF-alpha G/A308 gene and its association with nasal polyposis in north part of Iran. In this case-control study, 60 patients with NP and 75 healthy individuals referred to Guilan University hospital were evaluated. After DNA extraction, RFLP-PCR was used to determine polymorphism. Chi-square test was used to compare the frequency distribution of genotype and alleles of TNF-alpha gene with NP. The frequency of genotype G/G, A/A and G/A in the NP group was 46.7, 10.0 and 43.3%, and in the control group was 65.3, 5.3 and 29.3%, respectively. There was a statistically significant difference between genotype G/G in two groups (P = 0.006, OR 2.58, CI 1.27-5.23). In addition, the frequency of allele A in patients and controls was 31.7 and 20%, respectively; and this difference was statistically significant (p = 0.02). The findings of this study demonstrated that polymorphism in TNF-alpha gene might be a risk factor for NP in north part of Iran and the minor frequency of G308A allele in the current study is slightly more than other major populations. However, more investigations with high number of population are necessary in future.

The role of TNF alpha polymorphism and expression in susceptibility to nasal polyposis

ABSTRACTObjective: In this study, we first performed a meta-analysis to assess the role of single-nucleotide polymorphism (SNP) within tumor necrosis factor alpha (TNF alpha) gene and TNF alpha expression in the risk of nasal polyposis.Methods: STATA 12.0 software was utilized to conduct the Mantel–Haenszel statistics, Cohen statistics, Begg’s test, Egger’s tests and sensitivity analysis.Results: We systemically carried out the database retrieval and initially identified 486 articles. After screening, 15 articles were included in our meta-analysis. For TNF alpha rs1800629 G/A SNP, compared with control group, an increased risk of nasal polyposis of case group was observed in the models of A vs. G [p (P value of association) = 0.009, OR (odds ratio) = 1.35], GA vs. GG (p = 0.001, OR = 1.69), GA+AA vs. GG (p = 0.010, OR = 1.47). The similar results were observed in Caucasian subgroup (p < 0.05, OR > 1). For TNF alpha rs361525 G/A SNP, no significant difference between control and case group was detected (all p > 0.05). In addition, a significant difference exists between case and control groups in the meta-analyses of TNF alpha expression in nasal mucosal cells, secreted TNF alpha (p < 0.05, OR > 1), but not serum TNF alpha (p = 0.090).Conclusion: The present meta-analysis revealed that TNF alpha rs1800629, increased TNF alpha expression and secretion of nasal mucosal cells were associated with an increased risk of nasal polyposis.