Association Of Tumor Necrosis Factor-alpha Research Articles

Association of Tumor Necrosis Factor-Alpha, Interleukin-1β, Interleukin-8, and Interferon-γ with Obstructive Sleep Apnea in Both Children and Adults: A Meta-Analysis of 102 Articles.

Background: Cytokines may have a significant impact on sleep regulation. In this meta-analysis, we present the serum/plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8, IL-1β, and interferon-gamma (IFN-γ) in both children and adults with obstructive sleep apnea (OSA) in comparison to controls. Methods: Four electronic databases were systematically searched (PubMed, Web of Science, Scopus, and Cochrane Library) through 19 October 2023, without any restrictions on language, date, age, and sex. We used Review Manager version 5.3 to perform meta-analysis and presented the data as standardized mean difference (SMD) and 95% confidence interval (CI) values to evaluate the relationships between the levels of cytokines and OSA. Results: A total of 102 articles (150 independent studies) were included in the meta-analysis. The pooled SMDs in adults were 1.42 (95%CI: 1.11, 1.73; p < 0.00001), 0.85 (95%CI: 0.40, 1.31; p = 0.0002), 0.69 (95%CI: 0.22, 1.16; p = 0.004), and 0.39 (95%CI: -0.37, 1.16; p = 0.31) for TNF-α, IL-8, IL-1β, and IFN-γ, respectively. The pooled SMDs in children were 0.84 (95%CI: 0.35, 1.33; p = 0.0008), 0.60 (95%CI: 0.46, 0.74; p < 0.00001), 0.25 (95%CI: -0.44, 0.93; p = 0.49), and 3.70 (95%CI: 0.75, 6.65; p = 0.01) for TNF-α, IL-8, IL-1β, and IFN-γ, respectively. Conclusions: The levels of proinflammatory cytokines of TNF-α, IL-8, and IL-1β in adults, and TNF-α, IL-8, and IFN-γ in children with OSA, are significantly higher than those in controls.

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia.

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=-0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=-0.258, t=-2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=-0.247, p=0.019) and antipsychotic treatment duration (ρ=-0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.

Association of Tumor Necrosis Factor-Alpha (TNF-α) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

Abstract Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-α (TNF-α) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA &gt; Del) and TNF-α (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19). Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups. Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p &lt; 0.05). The GG genotype of the TNF-α was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-α was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold). Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes.

Is there an association between inflammatory markers and lower physical performance in older adults?

BackgroundMaintenance of physical performance is essential for achievement of healthy aging. A few studies have explored the association between inflammatory markers and physical performance in older adults with inconclusive results. Our aim was to analyze the association of tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), and C-reactive protein (CRP) with physical performance in a sample of older adults in rural settings of Mexico.MethodsOur study comprised 307 community-dwelling older men and women who participated in the third wave of the Rural Frailty Study. We assessed the physical performance with the Short Physical Performance Battery (SPPB) and classified older adults as low performance if SPPB scored ≤8. Inflammatory markers were ascertained using serum by immunodetection methods. Logistic regression models were used to estimate the associations between inflammatory markers and physical performance.ResultsIn comparison with the normal physical performance group, low physical performance individuals mainly were female (P < 0.01), older (P < 0.01), more illiterate (P = 0.02), more hypertensive (P < 0.01), fewer smokers (P = 0.02), and had higher CRP levels (P < 0.01). The logistic model results showed a significant association between the 3rd tertile of CRP and low physical performance (OR = 2.23; P = 0.03). IL-10 and TNF-α levels did not show a significant association.ConclusionsThe results of this study were mixed, with a significant association of physical performance with higher CRP levels but nonsignificant with IL-10 and TNF-α. Further studies with improved designs are needed by incorporating a broader set of inflammatory markers.

Association of tumor necrosis factor-alpha and interleukin-10 levels with ultrasound characteristics of atherosclerotic plaques in patients with essential hypertension

Aim. To study the association of ultrasound characteristics of carotid atherosclerotic plaques (ASPs) with the concentration of tumor necrosis factor-alpha (TNFα) and interleukin-10 (IL-10) in patients with essential hypertension.Material and methods. The study included 117 patients (men, 75; women, 42) with essential hypertension aged 40 to 75 years (mean age, 55,8±7,5 years). All patients underwent anthropometric measurements (height, weight, body mass index, waist circumference), assessment of blood pressure and heart rate, blood tests (levels of glucose, creatinine with the calculation of glomerular filtration rate using CKD-EPI equation, lipid profile), duplex ultrasound of the carotid arteries. Also, the blood concentration of TNFα and IL-10 by the enzyme-linked immunosorbent assay using CYTOKIN-STIMUL-BEST (Novosibirsk,Russia) kit was determined.Results. According to the results of carotid duplex ultrasound, 3 groups of patients were identified. Group 1 included 48 patients with homogeneous hyperechoic ASPs; group 2 — 56 patients with dominant hyperechoic ASPs (&gt;50% of areas); group 3 — 13 patients with anechoic, unstable, low-density ASPs. TNFα concentration in group 3 patients, amounting to 10,51±2.23 pg/ml, was significantly higher than in patients of group 1 (7,26±0,64 pg/ml (p&lt;0,001)) and group 2 (8,93±0,98 pg/ml (p&lt;0,001)). Similar results were obtained for IL-10. The logistic regression showed that the TNFα concentration is an independent factor associated with unstable ASsP (relative risk, 2,72; 95% confidence interval 1,44-5,15 (p&lt;0,02)). It was also revealed that TNFα &gt;10 pg/ml increased the risk of ASP instability by ~8 times.Conclusion. An increase in TNFα &gt;10 pg/ml with a high specificity (95%) was associated with vulnerable unstable carotid ASPs.

Association of tumor necrosis factor-alpha and lipid parameters in patients with coronary heart disease and heart failure

Background and Aims: Among the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) is a key player maintaining low-level systemic inflammation. Several mechanisms were described that contribute to the proatherogenic effects of TNF-α. Aim: to investigate the association between TNF-α and lipid parameters in patients with coronary heart disease (CHD) and heart failure (HF).

Association of tumor necrosis factor-α and -β gene polymorphisms in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this case–control study was to evaluate the association of tumor necrosis factor-alpha (TNF-α) (308) and -β (+252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) =84 and Crohn’s disease (CD) =95) and 200 age- and sex-matched healthy controls were recruited. TNF-α and TNF-β genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-α (−308) and -β (+252) polymorphisms. The frequency of the GA genotype of TNF-α (−308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-α (−308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-β (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-β was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-α and-β polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms are associated with risk of developing IBD in Saudi population.

Association of Tumor Necrosis Factor-alpha and Interleukin-6 Gene Polymorphisms with Preeclampsia

Preeclampsia is a pregnancy-specific syndrome that may be dangerous especially to the fetus. Different cytokines have been found to be elevated in women with preeclampsia and may have possible roles in the development of this disorder. Alleles of the interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) genes are associated with preeclampsia in several studies in different populations. The aim of the present study was to investigate the relationship between IL-6 (G174C) and TNF-α (G-308A) gene polymorphisms with preeclampsia in North Coastal Andhra Pradesh of India. The TNFA (-308 A/G) and IL6 (-674G/C) genotypes were determined in 100 preeclamptic women and 100 normal pregnant women as control group, using allele-specific oligonucleotides-polymerase chain reaction method. Data was analyzed using chi-square and Fisher’s exact tests. TNF-α (G-308A) G/G genotype showed a significantly higher frequency among the preeclamptic group than the control group (odds ratio, 0.4603, 95% confidence interval, (0.2521- 0.8405); P = .005). G/A genotype also showed higher frequency among the preeclamptic group compared to control group (odds ratio, 2.508, 95% confidence interval, ((1.341-4.689); P = .001). IL-6 (G174C) genotype significantly higher frequency among the preeclamptic group than the control group (odds ratio, 0.4603, 95% confidence interval, (0.2521- 0.8405); P = .005). The present study might suggest a role for TNF-α (G-308A) and -174 GC of IL-6 genotype in the development of preeclampsia; suggesting that they are of differing genetic predisposition/pathophysiology.

Association of tumor necrosis factor-alpha 308G/A polymorphism with recurrent miscarriages in women.

BACKGROUND:Recurrent miscarriage (RM) is the most common pregnancy loss in the first trimester affecting approximately 0.5–2% of women. It is a heterogeneous condition and remains an enigma as the underlying cause is still difficult to track down.AIM:This study was aimed to investigate the distribution of tumor necrosis factor-alpha (TNF-α) 308G/A polymorphism and its association with RM in females. The comparative picture was also demonstrated by comparing genotyping results with healthy control women having no history of miscarriage.METHODS:This clinical study was conducted among 115 women aged 21–44 years with history of recurrence of miscarriage. The samples were collected from women attending the outpatient departments of various hospitals, nursing homes, and infertility clinics of this region. In the present study, 111 fertile healthy women aged 24–46 years with at least one live birth and no history of miscarriage were also included.RESULTS:Mean age of women with RM was found to be 28 ± 5.6 years by recall method, whereas it was found to be 30 ± 7.4 in context to healthy women with no history of pregnancy loss. In the present study, 66% of women with RM had homozygous wild type genotype (GG) while 30% and 4% of women had heterozygous (GA) and homozygous mutant genotype (AA), respectively. Among control group, 79%, 16%, and 5% of women showed GG, GA, and AA genotype, respectively.CONCLUSION:The current study supports the concept of TNF-α 308G/A variant in particular with reproductive failure, GG and GA alleles showing 1-fold risk association with RM (odds ratio: 1.86 and 1.43, respectively).

Association of tumor necrosis factor-alpha and interferon gamma gene polymorphisms and their plasma levels in leprosy, HIV and other peripheral neuropathies

ObjectiveMycobacterium leprae and Human Immunodeficiency Virus (HIV) are causative agents known to be involved in nerve damage in leprosy and HIV-peripheral neuropathy (HIV-PN) respectively. Among other peripheral neuropathies the most common is diabetic neuropathy, which is metabolically induced. The proinflammatory cytokines TNF-α and IFN-γ have been implicated in the pathogenesis of peripheral neuropathy. The association between the plasma levels of these cytokines and their single nucleotide polymorphisms (SNPs) were investigated in leprosy neuropathy (LN), HIV-PN and other peripheral neuropathies (OPN). MethodsEighty-eight individuals with LN (PB=36; MB=52), 39 with HIV-PN, 52 patients with OPN, 101 HIV positive individuals without neuropathy (HIV) and 113 healthy subjects (HS) were included in the study. Plasma cytokine levels were measured by sandwich ELISA and one way ANOVA was carried out among the groups. SNPs of TNF-α- 308 G/A, −238 G/A and IFN-γ +874 T/A were investigated by amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Their frequencies were compared between groups by Pearson’s chi squared test. ResultsPlasma TNF-α and IFN-γ was significantly increased in LN (p<0.05), HIV-PN (p<0.05) and OPN (p<0.05) as compared to HS. A significant association was found between IFN-γ +874 A/A genotype in LN (p<0.05; OR=7.9), HIV-PN (p<0.05; OR=8.9) and OPN (p<0.05; OR=8.9) as compared to HS. ConclusionElevated levels of plasma TNF-α and IFN-γ and the association of IFN-γ +874 A/A genotype SNP in LN, HIV-PN and OPN suggests a common involvement of these cytokines in susceptibility/pathogenesis of peripheral neuropathy.

Association of the tumor necrosis factor-alpha -1031T/C and its combination with interleukin-6 -634C/G gene polymorphisms with susceptibility to endometriosis

To investigate the association of tumor necrosis factor-alpha (TNF-α) gene promoter region -1031T/C and its combination with interleukin-6 (IL-6) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the genetic susceptibility to endometriosis. Total of 432 endometriosis patients and 499 non-endometriosis women who had received an operation due to tubal ligation, tubal recanalization, laparoscopic hydrotubation, ovarian simple cyst and teratoma were collected and separated into endometriosis group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in endometriosis and control group to evaluate the association of these SNP with the susceptibility to endometriosis by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. (1) TNF-α -1031T/C genotype:the T and C of TNF-α -1031T/C allele frequencies in the endometriosis group and control group were 79.2% (684/864), 20.8% (180/864) and 81.8% (816/998), 18.2% (182/998), respectively. The TT, TC and CC of TNF-α -1031T/C genotype frequencies in the two groups were 63.7% (275/432), 31.0% (134/432), 5.3% (23/432) and 66.5% (332/499), 30.5% (152/499), 3.0% (15/499), respectively. There were no statistical significances in the TNF-α -1031T/C alleles and genotypes distributions between the two groups (P = 0.158, P = 0.186). (2) TNF-α -1031T/C and IL-6 -634C/G conjoint genotypes: to research on the TNF-α -1031T/C and IL-6 -634C/G genotypes for conjoint analysis, the TT+CC, TC+CC, CC+CC, TT+CG, TC+CG, CC+CG, TT+GG, TC+GG and CC+GG combination genotype frequencies in the two groups were 39.4% (170/432), 19.4% (84/432), 4.6% (20/432), 20.6% (89/432), 8.8% (38/432), 0.9% (4/432), 3.5% (15/432), 2.3% (10/432), 0.5% (2/432) and 36.7% (183/499), 17.4% (87/499), 1.4% (7/499), 26.1% (130/499), 10.4% (52/499), 1.2% (6/499), 3.8% (19/499), 2.6% (13/499), 0.4% (2/499), respectively. There were no statistical significances in the combination genotypes distributions between the two groups (P = 0.107). As compared with carriers of TT+CC combination genotype, the endometriosis risk of carriers of CC+CC combination genotype enhanced 3.076 times (95%CI: 1.268 - 7.457, P = 0.009), and the endometriosis risk of carriers of other combination genotypes were no statistical significances (all P > 0.05). The study demonstrates that there are no significant association between the SNP of TNF-α -1031T/C and genetic susceptibility to endometriosis. However the results indicate that there are significant association between genetic susceptibility to endometriosis and the combination polymorphisms of TNF-α -1031T/C and IL-6 -634C/G.

Association of tumour necrosis factor-alpha −308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis

The objective was to analyze the possible involvement of tumour necrosis factor-alpha (TNF-α) -308 G/A promoter polymorphism in the susceptibility and/or the disease profile of rheumatoid arthritis (RA) in Egyptian patients. TNF-α-308 G/promoter polymorphism detection by amplification refractory mutation system (ARMS) technique was carried out for 122 RA patients and 120 healthy controls. TNF-α-308 G allele/GG homozygous genotype were higher in patients with rheumatoid arthritis than those in control group (P < 0.001, respectively). A statistically significant association was found between the frequency of the A allele and presence of erosion (OR = 3.42, P = 0.015). No associations were found between the distribution of TNF-α-308 G/A alleles/genotypes and age of patients, disease duration, absence of remission, presence of deformity, clinical manifestations of the disease and presence or absence of rheumatoid factor. The positivity of rheumatoid factor was associated with occurrence of erosion (OR = 25.0, P < 0.001). The results of this study demonstrate the association of the TNF-α-308 G allele and GG homozygous genotype with susceptibility to RA and the A allele with the presence of erosion in the Egyptian patients.

Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults

T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were gender-matched (1∶3) with healthy controls from the Wellcome Trust Case Control Consortium. Variants IL10 −819 c>t, TNFA −308 g>a, TGFB1 −509 c>t, IL1A −889 c>t, IL10 −592 c>t, and IL4R q576r were measured in cases and retrieved for controls from the European Genome-phenome Archive. Associations were evaluated using logistic regression models. In total, 206 patients with primary ITP were matched with 618 controls. A significant per allele odds ratio of 1·34 (95% confidence interval, 1·03–1·75; P = 0·03) was observed for TNFA −308 g>a, implicating an increased disease susceptibility among Caucasian carriers of the rare allele.

Tumor necrosis factor-α polymorphisms in women with idiopathic recurrent miscarriage

We investigated the association of tumor necrosis factor-alpha (TNFalpha) gene polymorphisms with idiopathic recurrent miscarriage (RM). TNFalpha -1031T/C, -863C/A, -857C/T, -376G/A, -308G/A, -238G/A, and +488G/A single nucleotide polymorphisms (SNPs) were investigated in 204 RM women and 248 age-matched parous women by PCR-restriction fragment length polymorphism. Significantly higher frequencies of -1031C and -376A alleles were seen in RM patients; significant differences were also noted in the distribution of -1031T/C, -376G/A, and -238G/A genotypes between case and control subjects. Haploview analysis revealed high linkage disequilibrium between -857C/T and +488G/A SNPs, but was lower between the other polymorphisms. Of the possible 52 seven-locus haplotypes constructed, 10 were common, and were included in subsequent analysis. Increased frequency of CCCGGGG and CCCGGAA haplotypes, and reduced frequency of TCCGGGG and TCCGGGA haplotypes were seen in RM patients than in controls. When the Bonferroni correction was applied, differences were significant for the CCCGGAA haplotype, which was higher (OR=4.14; 95% CI=1.84-8.95), and the TCCGGGA haplotype, which were lower among RM cases (OR=0.09; 95% CI=0.02-0.68), thereby conferring RM susceptibility and protection to these haplotypes, respectively. Multivariate analysis confirmed the positive association of only CCCGGAA haplotype with RM (P=0.010; aOR=2.03; 95% CI=1.18-4.47), after controlling for a number of covariates. These results demonstrate that the TNFalpha polymorphisms, in particular the -1031T/C variant, are significantly associated with idiopathic RM. Additional replication studies on other racial groups are needed to confirm our findings.

P40 Lack of association of tumour necrosis factor-alpha (TNF-α) promoter polymorphism in systemic lupus erythematosus patients of South Indian Tamil ethnic population

P40 Lack of association of tumour necrosis factor-alpha (TNF-α) promoter polymorphism in systemic lupus erythematosus patients of South Indian Tamil ethnic population

Coronary artery calcification, arterial stiffness and renal insufficiency associate with serum levels of tumor necrosis factor-alpha in Japanese type 2 diabetic patients

Although the kidneys are the major source of proinflammatory cytokines, association of tumor necrosis factor-alpha (TNF-α) with severity of atherosclerosis or kidney function in diabetic patients is unclear. Two hundred type 2 diabetic patients and 30 age-matched nondiabetic subjects consecutively admitted to our hospital were enrolled. The Agatston coronary artery calcium score (CACS), a quantitative marker of coronary atherosclerosis, was obtained using multidetector-row computed tomography. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Diabetic patients had higher log(CACS + 1) ( p = 0.0089), baPWV ( p = 0.0293), frequency of elevated urinary albumin excretion (UAE) ( p < 0.0001) and TNF-α ( p = 0.0029) and similar estimated glomerular filtration rate (eGFR) compared to nondiabetic subjects. When diabetic patients were grouped into four subgroups with or without elevated UAE and renal insufficiency (UAE of ≥30 or <30 mg/24 h and eGFR of <60 or ≥60 ml/min per 1.73 m 2), patients with micro- and macroalbuminuric renal insufficiency showed the highest log(CACS + 1) ( p < 0.0001), baPWV ( p = 0.0068) and TNF-α ( p < 0.0001) of these groups. Log(CACS + 1) ( p = 0.0008) and baPWV ( p = 0.0006) positively and eGFR ( p < 0.0001) negatively correlated with TNF-α in diabetic patients. We find that coronary artery calcification, arterial stiffness, and renal insufficiency associate with circulating levels of TNF-α in type 2 diabetic patients.

Tumor necrosis factor‐α promoter polymorphism is associated with the risk of Parkinson's disease

Inflammatory events may contribute to the pathogenesis of Parkinson's disease (PD). We conducted a case-control study in a cohort of 369 PD cases and another cohort of 326 ethnically matched controls to investigate the association of tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphisms (SNPs) with the risk of PD. The overall genotype distribution at T-1031C and C-857T sites showed significant difference between PD cases and controls (P = 0.0062 and 0.0035, respectively). However, only the more frequent -1031 CC genotype was evidently associated with PD (P = 0.0085, odds ratio: 2.96; 95% CI: 1.38-7.09). Pairwise SNP linkage disequilibrium showed -1031 and -863 sites are in strong linkage disequilibrium (D' = 0.93, Delta(2) = 0.80). Pairwise haplotype analysis among the four sites showed that -1031C-863A may act as a risk haplotype among PD cases (P = 0.0028, odds ratio: 2.18; 95% CI: 1.33-3.69).

Analysis of association between maternal tumor necrosis factor-α promoter polymorphism (–308), tumor necrosis factor concentration, and preterm birth

This study was undertaken to investigate the association of tumor necrosis factor-alpha (TNF-alpha) single nucleotide polymorphism (G-308>A) and risk of preterm birth by performing a systematic review and a meta-analysis of available studies. In addition, association between this variant and TNF-alpha concentration in amniotic fluid (AF) in preterm birth was also investigated. Articles were chosen based on a Medline and EMBASE searches (1990-2005) with no language restrictions. An ongoing case-control study conducted in Nashville, TN, was also included. Articles evaluating the association between G-308>A and preterm birth were screened according to specific inclusion criteria. Meta-analysis was performed by using a random effect model. Association between maternal -308 genotype and AF-TNF-alpha concentration was determined by sandwich immunoassays. Titles and abstracts of 6851 citations identified through the search were screened. Including our own study, a total of 7 studies were included for meta-analysis. Only 2 reported a statistically significant increased risk based on -308 genotype. Meta-analysis of the case-control studies on a pooled dataset (a total of 1846 subjects, 638 cases, and 1208 controls) showed no significant association between the -308 genotype and the risk of preterm birth (odds ratio [OR] 1.41; CI 0.90-2.19). A nonsignificant increase of AF TNF-alpha concentration was demonstrated with the GG genotype in cases compared with the presence of allele A. Meta-analysis of available evidence documented no statistically significant association between a single nucleotide polymorphism in the TNF-alpha gene (G-308>A) and preterm birth. Analyses of AF-TNF-alpha concentration demonstrated no increase in TNF-alpha in the presence of the minor allele (A). These results suggest that this single nucleotide polymorphism does not independently associate strongly with preterm birth.

The G-308A promoter variant of the tumor necrosis factor-alpha gene is associated with migraine without aura

Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. Tumor necrosis factor-alpha (TNF-alpha), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes in brain. The hypothesis of this study was that migraine without aura (MWA) might be associated with TNF-alpha (-308) polymorphism, resulting in increased TNF-alpha production. Genotyping was performed on DNA extracted from peripheral leukocytes by PCR-SSP method in 221 patients with WMA and 183 healthy control subjects from Iranian population. The results showed that the frequency of -308 A variant allele was higher in MWA than in the control group (40.6% versus 22.3%, OR 3.73, 95% CI 2.4-5.82, p<0.0001). TNF-alpha GA heterozygous genotype, high producer, was significantly more prevalent in patients with MWA than controls (74% versus 44.7%, p<0.0001) whilst the low producer GG homozygous genotype was less frequent in patients compared with controls (22.4% versus 55.3%, p<0.0001). The logistic regression analysis showed a significant association for TNF-alpha (-308A) female allele carriers with MWA at reproductive ages (OR 2.56; 95% CI, 1.57-4.16, p<0.0001) when compared with their matched control subjects. In conclusion, this study demonstrates an association of tumor necrosis factor-alpha (-308A) carriage with MWA, suggesting that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop MWA.

Association of Tumor Necrosis Factor-alpha; and Neutrophilic Inflammation in Severe Asthma

Association of Tumor Necrosis Factor-alpha; and Neutrophilic Inflammation in Severe Asthma