TNF-α Genotypes Research Articles

Association of tumor necrosis factor-alpha gene promoter polymorphism and its mRNA expression level in coronary artery disease

Backgroundumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that may play an important role in inflammatory diseases like coronary artery disease (CAD). As a result of controversy on the impact of polymorphisms in the promoter region of TNF-α gene on transcription, this case control study was designed to evaluate the effects of TNF-α -308G > A (rs1800629) and TNF-α − 238G > A (rs361525) on mRNA expression level and risk of CAD. MethodsOverall, 379 patients with CAD and 461 healthy controls participated in this study. Subjects were matched in terms of age, sex and ethnic origin. Genotyping was performed using single specific primer-polymerase chain reaction (SSP-PCR) and TNF-α mRNA expression analysis was carried out by quantitative real time PCR. ResultsA/A and A/G genotypes in TNF-α (−308G > A) gene were significantly more frequent among patients than controls. The TNF-α (−238G > A) did not differ between CAD patients and controls (the TNF-α (−238G > A) genotypes and allele frequency showed no significant differences). Combination of AA TNF-α (−308) /GG TNF-α (−238) and AG TNF-α (−308) /AG TNF-α (−238) genotypes demonstrated higher frequencies in patients than in controls (P < .05). TNF-α mRNA expression level showed significantly higher in patients carrying A/A genotype at TNF-α (−308) compared to healthy individuals. ConclusionAlthough there was no significant association between TNF-α -238 G > A polymorphism with TNF-α expression level and pathogenesis of CAD in the studied population, The TNF-α (−308G > A) gene polymorphism was associated with its expression and development of CAD.

Opisthorchiasis with proinflammatory cytokines (IL-1\u03b2 and TNF-\u03b1) polymorphisms influence risk of intrahepatic cholangiocarcinoma in Thailand: a nested case-control study

BackgroundChronic inflammation and repeated infection with Opisthorchis viverrini (O. viverrini) induces intrahepatic cholangiocarcinoma (ICC). Inflammatory cytokines such as interleukin (IL) and tumor necrosis factor (TNF) are substances in the immune system that promote inflammation and causes disease to progress. Genes that help express proinflammatory cytokines can affect an individual’s susceptibility to disease, especially in cancer-related chronic inflammation. This study aimed to investigate risk factors for ICC with a focus on opisthorchiasis and polymorphisms of proinflammatory cytokines (IL-1β and TNF-α).MethodsThis study was a nested case-control study within a cohort study. 219 subjects who developed a primary ICC were identified and matched with two non-cancer controls from the same cohort based on sex and age at recruitment (±3 years). An O. viverrini-IgG antibody was assessed using enzyme linked immunosorbent assay. IL-1β and TNF-α polymorphisms were analyzed using a polymerase chain reaction with high resolution melting analysis. Associations between variables and ICC were assessed using conditional logistic regression.ResultsSubjects with a high infection intensity had higher risk of ICC than those who had a low level (OR = 2.1; 95% CI: 1.2–3.9). Subjects with all genotypes of TNF-α (GG, GA, AA) and high infection intensity were significantly related to an increased risk of ICC (p < 0.05).ConclusionsPolymorphisms of IL-1β and TNF-α are not a risk of ICC, but an individual with O. viverrini infection has an effect on all genotypes of the TNF-α gene that might promote ICC. Primary prevention of ICC in high-risk areas is based on efforts to reduce O. viverrini infection.

Significant association of TNF-α, but not other pro-inflammatory cytokines, single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population

ObjectivesAs the important role of inflammation in pathophysiology of intervertebral disc degeneration and inconsistency regarding the role of pro-inflammatory cytokine genes SNPs, the current case-control study was designed to assess this in Iranian population. Patients and MethodsThe genomic DNA of peripheral leukocytes of 76 patients and 140 healthy controls were investigated to sequence 9 SNPs of pro-inflammatory cytokine genes of interleukin 1 (IL-1), interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF-α) family. Results‘GA’ and ‘GG’ genotype of TNF-α −308 G/A SNP were significantly associated with IVDD. While ‘GA’ was 1.93 times more frequent in patients, the ‘GG’ genotype was more common among healthy subjects (OR = 0.51, P = 0.03). The ‘G’ allele of TNF-α −238 G/A was 2.51 times more common in IVDD patients while the ‘A’ genotype was more frequent in controls with odds ratio of 0.39 (P = 0.001). Interestingly, the homozygote ‘GG’ genotype was 2.98 times more prevalent in patients (P = 0.001) while the ‘GA’ heterozygote genotype was more common in healthy individuals (OR = 0.34). The other investigated SNPs were not significantly associated with disease in this study population. ConclusionPolymorphisms of pro-inflammatory cytokine genes could take part in IVDD pathophysiology as the result of alteration in their expression levels or structures. The current study indicated significant roles of TNF-α −308 G/A and TNF-α −238 G/A SNPs with IVDD among Iranian patients. However, this study did not show any significant association between IVDD and either of SNPs of IL-1 and IL-6 genes.

The impact of TNF-α 308G>A gene polymorphism on children’s overweight risk and an assessment of biochemical variables: A cross-sectional single-center experience

The aim of this study was to assess the role of TNF-α 308 G>A gene polymorphism in children's overweight risk so as to correlate this polymorphism with anthropometric and biochemical variables. A cross-sectional study was carried out on 188 Romanian children ages 5-18 years, who were classified into controls (Group 1; n=109) and overweight children (Group 2; n=79). Higher values of MUAC and TST (p<0.001) were obtained in the overweight group. A significant association was found between TNF-α 308G>A polymorphism and weight status in the studied population (p=0.009). There was also a positive association between the variant genotypes (GA or AA) of TNF-α 308G>A gene polymorphism and weight status, which was more frequently found among normal weight than overweight children (74.5% versus 25.5%, respectively). The final logistic multivariable included five independent variables (TNF-α genotype, gender, cholesterol, ASAT, and ALAT), which were statistically significant predictors with negative/positive effects on children's overweight risk; this model explained 30% of the variance in the outcome variable. The variant genotype of TNF-α 308G>A gene polymorphism was more frequent among normal weight children. In the presence of other covariates, such as age, gender, cholesterol, LDL cholesterol, ALAT, and glycemia, the TNF-α 308G>A gene polymorphism remained an independent protective factor for children's overweight status.

Association of TNF-α rs1799964 and IL-1β rs16944 polymorphisms with multiple system atrophy in Chinese Han population

ABSTRACTBackground: Recent evidence suggested that several single nucleotide polymorphisms (SNPs) of inflammation-related genes (TNF-α rs1799964, IL-1α rs1800587, IL-1β rs16944, IL-8 rs4073, ICAM-1 rs5498) were associated with multiple system atrophy (MSA). Herein, we conducted this case-control study to evaluate the possible correlation between the five SNPs related to inflammation and MSA in Chinese Han population.Methods and Patients: We recruited 154 sporadic patients with MSA and 223 health controls in this study. All subjects were genotyped for the five SNPs using polymerase chain reaction amplification and Sanger sequencing.Results: TNF-α rs1799964, genotype distribution and minor allele frequency (MAF) showed significant differences between patients and controls, which might illustrate the minor allele C may increase the risk for MSA (genotype, P = 0.006, OR = 1.245, 95% CI = [1.066–1.455]; allele, P = 0.001, OR = 1.887, 95% CI = [1.303–2.733]). For rs16944, patients carrying AA genotype showed a nearly 5-year early age at onset (AAO) than GG genotype (50.52 ± 7.45 years vs. 54.90 ± 7.21 years, P = 0.037). No differences were found in genotype distribution and MAF of the five SNPs between patients with MSA with predominant cerebellar ataxia (MSA-C) and with predominant Parkinsonism (MSA-P).Conclusion: Our study suggests that rs1799964 of TNF-α may act as a risk factor for MSA and the IL-1β rs16944 might be a genetic factor that modifies the AAO in MSA. Moreover, the exact mechanism of neuroinflammatory response in MSA deserves further exploration.

TNFA gene in Brazilian patients with hemorrhagic stroke and cerebral aneurysm

ABSTRACT Introduction: Many cerebrovascular diseases display a relation with inflammatory processes. Furthermore, the influence of several polymorphisms has been studied to improve the knowledge of physiological mechanisms of the nervous system. Objectives: The aim of this study was to identify if there was an association between a polymorphism in -308 position of the TNFA gene and the development of hemorrhagic stroke or aneurysm in Distrito Federal, Brazil. Methods: We collected the clinical information and the medical records from hemorrhagic stroke or aneurysm patients. The occurrence of stroke or aneurysm was confirmed by computed tomography (CT) or magnetic resonance image (MRI). The TNFA genotypes were determined by polymerase chain reaction restriction fragment length polymorphism. Results: The AG genotype appears to decrease the occurrence of hemorrhagic stroke or aneurysm in people between 45-63 years. Our study was the first to investigate this association in a Brazilian sample, although a previous report showed a similar effect with ischemic stroke in a Chinese population. Conclusion: The TNFA -308 AG genotype is associated with a decreased risk of aneurysm or hemorrhagic stroke in a population from the capital of Brazil, Distrito Federal.

Молекулярно-генетические аспекты исследования полиморфизма генов цитокиновой сети у больных спаечной болезнью брюшины

With the aim of studying the genetic aspects of the pathogenesis of adhesive disease polymorphism of genes of cytokines TNF-a, IL-1 p, IL-6 polymerase chain reaction DNA synthesis is determined and estimation of clinical-genetic associations in predicting risk of disease is made. Genetic markers of susceptibility to the development of adhesive disease peritoneum are genotype of GG polymorphic locus-308G > A TNF-a gene (OR = 1.914) allele (T) polymorphic locus-511C > T gene IL-1 p (OR = 1.700) and genotype of CC polymorphic locus-174 g > C gene IL-6 (OR = 2.554). Markers of resistance to adhesive disease development of the peritoneum are genotype of GA polymorphic locus-308G > A TNF-a gene (OR = 0.462), genotype and allele with polymorphic locus-511C > T (OR = 0.510 and Or = 0.589).

Association of the TNF-α, IL-2, and IL-2RB gene variants with susceptibility to psoriasis in a Turkish cohort.

Aim of the studyThe aim of this study was to investigate the role TNF-α, IL-2, and IL-2RB variants in psoriasis (Ps) and to evaluate the association between these variants and clinical features.Material and methodsA total of 74 psoriatic patients and 74 healthy individuals were genotyped for these variants by PCR and/or RFLP.ResultsThe AA genotype of TNF-α (–308) was significantly more common in the patients (p = 0.013). TNF-α (–238) AA genotype was significantly increased in the patients (p = 0.028), while the GG genotype was decreased in the patient group, compared to the controls (p = 0.016). IL-2 (–330) variant GG and TT genotype was more common in the patients (p = 0.037, p = 0.009, respectively), while IL-2 (–330) GT genotype was increased in the control subjects (p = 0.001). IL-2 (–330) GG genotype frequency was significantly decreased (p = 0.021) and the TT genotype frequency was significantly increased among patients with psoriatic arthritis in comparison with Ps patients (p = 0.014). IL-2RB TC genotype frequency was significantly decreased and TT genotype frequency was significantly increased in the patients with positive family history of Ps compared to those who had a negative family history (p = 0.017, p = 0.014, respectively). Also, IL-2RB CC genotype was significantly increased among the patients with late-onset Ps in comparison with the early onset Ps group (p = 0.009). The frequency of IL-2 (–330) TT genotype was significantly higher in mild Ps patients than moderate-severe patients (p = 0.043).ConclusionsOur data suggest a potential role of these genes as candidate genes for susceptibility to Ps in a Turkish cohort.

Cytokine Gene Polymorphisms in Saudi Patients With Atopic Dermatitis: A Case-Control Study.

The cause of atopic dermatitis (AD) is multifactorial and a number of genes including cytokines have been involved. We genotyped 315 subjects for polymorphisms in TNF-α and TNF-β and IL-10 genes. Patients had significantly higher frequency of GA genotype of TNF-α (−308 G/A) than healthy controls. Patients with AD and controls had similar distribution of A and G alleles. Genotype AA was found in 7.11% of controls while completely absent in cases. The frequencies of genotypes GG and AA of TNF-β (+252 A/G) polymorphism were higher whereas the frequency of genotype GA was significantly lower in patients than the controls. The frequencies of genotypes GG and AA of IL-10 (1082 G/A) polymorphism were significantly increased whereas genotype GA was decreased in patients than the controls. It is concluded that TNF-α (−308 G/A), TNF-β (+252 A/G), and IL-10 (−1082 G/A) polymorphisms are linked with the susceptibility of AD in Saudis and can be a risk factor.

Associations of Tumor Necrosis Factor–α and Interleukin-1β Levels and Polymorphisms with Post-Stroke Depression

Proinflammatory cytokines have been implicated in the pathophysiology of post-stroke depression (PSD), and their production levels are influenced by the transcriptional activity of genetic polymorphisms. The present study aimed to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the serum on the risk of PSD while taking into account the TNF-α -850C/T and -308G/A polymorphisms and the IL-1β -511C/T and +3953C/T polymorphisms. A total of 286 patients were evaluated at 2 weeks post stroke and 222 (78%) of these patients were followed up 1 year later. Depressive (major or minor) disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria during both examinations; evaluations of cytokine concentrations and polymorphisms and demographic and clinical covariates were performed at 2 weeks. The effects of TNF-α and IL-1β concentrations and genotypes on PSD status were investigated using multivariate logistic regression models. Higher TNF-α levels were associated with PSD at 2 weeks in the presence of the -850T allele with a significant interaction term; higher IL-1β levels were associated with PSD at 2 weeks in the presence of the -511T allele with a borderline significant interaction term and with any +3953C/T polymorphism without a significant interaction term. No associations were found with PSD at 1 year. These findings indicate the important roles that TNF-α and IL-1β serum levels play regarding the risk of PSD, particularly during the acute phase of stroke and in patients with genetic susceptibility.

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia.

BackgroundSchizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia.ObjectiveThe aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF)-α (−308G/A) and TNF-β (+252A/G) polymorphisms with schizophrenia susceptibility.Subjects and methodsTNF-α and TNF-β genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms in patients were compared with those in controls.ResultsThe frequencies of TNF-α (−308) allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (−308G/A) may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-β (+252A/G) polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-β (+252A/G) was significantly higher in male patients than in female patients. The distribution of TNF-α (−308G/A) and TNF-β (+252A/G) polymorphisms was almost similar in schizophrenia patients with negative or positive symptoms.ConclusionTNF-α (−308G/A) and TNF-β (+252G/A) polymorphisms may increase the susceptibility to schizophrenia in Saudi patients and could be a potential risk factor for its etiopathogenesis. However, further studies are warranted involving a larger sample size to strengthen our findings.

Correlation of HLA-DQ and TNF-α gene polymorphisms with ocular myasthenia gravis combined with thyroid-associated ophthalmopathy.

The present study aims to explore the correlation of human leucocyte antigen (HLA)-DQ and tumour necrosis factor (TNF)-α gene polymorphisms with ocular myasthenia gravis (OMG) combined with thyroid-associated ophthalmopathy (TAO). From March 2009 to March 2015, 56 OMG patients complicated with TAO (OMG + TAO group), 134 patients diagnosed with OMG only (OMG group) and 236 healthy individuals (control group) were enrolled in the present study. PCR-sequence specific primer (PCR-SSP) was used for HLA-DQ genotyping and PCR-restriction fragment length polymorphism (PCR-RFLP) for TNF-α genotyping. ELISA kit was applied to detect acetylcholine receptor antibody (AchRAb) level and chemiluminescence immunoassay (CLIA) to measure thyroid-associated antibody (T-Ab) level. Logistic regression analysis was carried out to analyse the risk factors for OMG combined with TAO. DQA1*0103 showed lower frequency in the OMG group than in the control group. DQA1*0301 showed increased and DQB1*0601 showed decreased frequency in the OMG + TAO group. DQB1*0501 showed higher frequency in the OMG and OMG + TAO groups than in the control group. Patients carrying TNF-α -863C > A (CA + AA) might confront with greater risks of OMG combined with TAO. Frequency of DQA1*0103/*0301 and DQB1*0501/*0601, and TNF-α -863C > A, -238G > A and -308G > A were associated with the levels of AchRAb and T-Ab. TNF-α -863C > A (CA + AA) and high level of T-Ab were risk factors for OMG combined with TAO. Our results demonstrate that TNF-α -863 polymorphism is possibly correlated with the risk of OMG combined with TAO.

Prenatal Second-Hand Smoke Increases Atopic Dermatitis in Children withTNF-α/TLR4/GSTP1Polymorphisms

Although second-hand smoke (SHS) exposure is associated with asthma, its effect on eczema is unclear. Especially, the effect of maternal passive smoking on childhood eczema has rarely been studied. Polymorphisms in tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), and glutathione S-transferase P1 (GSTP1) genes interact with air pollutants and modify allergic disease development. This study aimed to investigate the effect of gene–environment interactions between SHS exposure and TNF-α/TLR4/GSTP1 polymorphisms on childhood eczema. From 2005 to 2006, 3,639 children aged 7 or 8 years were enrolled and followed up 2 years later. Details of SHS exposure and eczema were collected by questionnaires. TNF-α (rs1800629), TLR4 (rs1927911), and GSTP1 (rs1695) genotypes were determined. Maternal passive smoking during pregnancy was associated with increased prevalence of eczema diagnosis ever (adjusted odds ratio [aOR] 1.50, 95% confidence intervals [CI] 1.25–1.79), and eczema symptoms in the past 12 months...

Association of tumor necrosis factor-α -308 G/A gene polymorphism with coronary artery diseases: An evidence-based study.

Coronary artery disease (CAD) is the leading cause of death worldwide and remains a major health problem, providing the rationale for identification of molecular markers for detection of individuals at high risk of developing CAD. Tumor necrosis factor-α (TNF-α) plays a crucial role in the pathogenesis of CAD. We have therefore explored the association of TNF-α 308 (G/A) gene polymorphism in 903 individuals with/without CAD. TNF-α 308 gene polymorphism was analyzed in 903 subjects of whom 222 were healthy controls. Among the 681 patients who were investigated angiographically, 468 had ≧50% stenosis and 213 patients had <50% stenosis. Biochemical profiles (eg, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and CRP) were evaluated. Associations between TNF-α genotypes with biochemical and anthropometric characteristics were determined. The frequencies of TNF-α-AA or AG genotypes were significantly lower in patients classified as CAD patients with ≥ or <50% obstruction in at least one coronary artery, compared to the control group. We observed that CAD patients with ≥50% stenosis and with AA genotype were associated with higher risk of CAD with OR of 3.56 (95%CI: 1.02-12.41; P=.046) using multivariate analysis. Moreover, we found that TNF-α-308-AA genotype was associated with blood pressure and CRP level in CAD patients, compared to the wild type-genotype. Our data showed an association of TNF-α-308G/A polymorphism with CAD patients with ≥50% obstruction, supporting the need for further investigations on the role of TNF-α-308G/A polymorphism with hypertension.

The Synergistic Effect of TNFα -308 G/A and TGFβ1 -509 C/T Polymorphisms on Hepatic Fibrosis Progression in Hepatitis C Virus Genotype 4 Patients.

Tumor necrosis factor-alpha (TNFα) and transforming growth factor-beta (TGFβ1) cytokines are highly implicated in liver fibrosis. Polymorphisms in these cytokines affect their expression, secretion, and activity. This study aimed to evaluate the influence of TNFα -308 G/A and TGFβ1 -509 C/T polymorphism on hepatic fibrosis progression in Egyptian patients with hepatitis C virus (HCV) genotype 4. Genotyping of TNFα -308 G/A and TGFβ1 -509 C/T was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 122 subjects (50 healthy controls and 72 HCV patients). Also, serum TNFα and TGFβ1 levels were detected by enzyme-linked immunosorbent assay (ELISA). The genotyping results of early (F0-F1, n = 36) and late (F2-F4, n = 36) HCV fibrosis patients showed that late fibrosis patients had higher TNFα -308 AA genotype and TGFβ1 -509 TT genotype than early fibrosis patients (p = 0.016, 0.028, respectively). Moreover, the TNFα and TGFβ1 serum levels were significantly higher in HCV patients with TNFα A containing genotypes (GA+AA) (p = 0.004) and patients with TGFβ1 T containing genotypes (CT+TT) (p = 0.001), respectively. The combined unfavorable TNFα (GA/AA) and TGFβ1 (CT/TT) genotypes were highly associated with abnormal liver function parameters and were significantly higher in high activity (A2-A3) and late fibrosis (F2-F4) HCV patients (p = 0.023, 0.029). The multivariate analysis results confirmed that the combined TNFα-308 (AA) and TGFβ1 -509 (TT) unfavorable genotypes increased the risk of hepatic fibrosis progression by 6.4-fold than combined favorable genotypes (odds ratio: 6.417, 95% confidence interval [1.490-27.641], p = 0.013). In conclusion, both TNFα -308 G/A and TGFβ1 -509 C/T polymorphisms synergistically influence the hepatic fibrosis progression and can be used as potential biomarkers to predict hepatic disease progression in chronic hepatitis C patients.

Association between Interleukin-10-1082 G/A and Tumor Necrosis Factor-α308 G/A Gene Polymorphisms and Respiratory Distress Syndrome in Iranian Preterm Infants

Cytokine polymorphisms may contribute to the prevalence of respiratory distress syndrome. The present study was done to investigate the frequency of interleukin- (IL-) 10 and tumor necrosis factor- (TNF-) α gene polymorphisms and their association with the risk of RDS in preterm infants. One-hundred and nineteen patients with RDS and 119 healthy preterm infants were enrolled. PCR restriction fragment length polymorphism was used to determine the frequency of IL-10 and TNF-α genotypes at -1082 A and -308 A, respectively. One-hundred and nineteen out of 238 infants had RDS (50%). The age of the mothers and gestational age ranged 17–45 (mean: 28.6 ± 5.3) years and 24–34 (mean: 34.3 ± 2.38) weeks, respectively. Totally, 23 deaths were recorded in the RDS group. Incidence of TNF-α-308 A/A and TNF-α-308 G/A was 84% and 16%, respectively. TNF-a-308 G/G was not found in both groups. Prevalence of IL-10-1082 G/G and IL-10-1082 G/A variants was 65.5% and 34.5%, respectively. IL-10-1082 A/A was not found in both groups. The incidence of the allele G in the IL-10-1082 polymorphism was lower in RDS group (P < 0.05). We found that the risk of RDS was correlated to sex, gestational age, and IL-10-1082.

Association of TNF-α and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

Aim of the studyTo evaluate the role of potential genetic predictors –308G/A TNF-α and –403G/A CCL5 in treatment for HCV 1 genotype.Material and methodsTreatment results of 130 patients with chronic hepatitis C 1 genotype according to different genotypes of IL28B, CCL5, and TNF-α were analysed using multiple logistic regression.ResultsIL28B genotypes CC/CT/TT were found in 27 (20.8%), 74 (56.9%), and 29 (22.3%) patients. Genotypes GG/GA/AA of –308G/A TNF-α were revealed in 98 (75.4%), 30 (23.1%), and 2 (1.5%) patients. Genotypes GG/GA/AA of –403G/A CCL5 were revealed in 86 (66.2%), 39 (30%), and 5 (3.8%) patients, respectively. The previously known effect of IL28B was observed. IL28B TT genotype decreased end of treatment response (EOTR) rates by a factor of 29.0 (95% CI: 6.4-183). The combination of CCL5 GG and IL28B CT genotypes increased the risk of failure to achieve EOTR by a factor of 28.5 (95% CI: 7.2-160). Genotypes GA and AA of TNF-α (–308) G/A SNP increased the risk of relapse in patients who achieved EOTR (OR = 9.4; 95% CI: 2.4-48).ConclusionsPractitioners may benefit from using these predictors when considering indications for the antiviral therapy and deciding on the treatment regimen.

Tumor Necrosis Factor Alpha -308 G/A Single Nucleotide Polymorphism and Risk of Sperm Abnormalities in Iranian Males.

BackgroundSignaling molecules such as cytokines regulate spermatogenesis during the maturation of germ cells and sperm apoptosis. Tumor necrosis factor alpha (TNFα) is one of the most-documented cytokines that is involved in spermatogenesis. We investigated the association of the TNFα -308 G/A single nucleotide polymorphism with sperm abnormalities in Iranian males.Materials and MethodsThis case-control study included 180 infertile men who re- ferred to Yazd Research and Clinical Center for Infertility and 100 healthy normospermic controls. Infertile men were classified into four groups of azoospermia (n=91), oligospermia (n=26), teratospermia (n=30) and asthenoteratospermia (n=33). After sperm analysis, DNA was extracted from blood and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was carried out for the genotyping of TNFα- 308 G/A.ResultsThe A allele was significantly associated with sperm abnormality in our population [(P<0.001, odds ratios (OR) 95% confidence interval (CI)=2.31]. In addition, the A allele was also associated with azoospermia (P<0.001, OR (95% CI)=2.484), oligospermia (P=0.005, OR (95% CI)=2.51) and teratospemia (P<0.001, OR (95% CI)=3.385) but not with asthenoteratospermia (P=0.623).ConclusionOur data suggest that this single nucleotide polymorphism (SNP) maybe associated with the risk of sperm abnormality in infertile men of Iranian origin.

Tumor necrosis factor-α promoter gene polymorphism (308 G/A) in the Egyptian patients with systemic lupus erythematosus

Background Tumor necrosis factor-α (TNF-α) is a very important cytokine having different physiological and pathogenic effects that lead to tissue destruction. The polymorphism of the TNF-α promoter gene at position –308 has been thought as a genetic risk factor for systemic lupus erythematosus (SLE). Thus, we aimed in this study to evaluate the association between TNF-α gene polymorphism (308 G/A) and SLE in the Egyptian population and its relation to the activity and the clinical manifestations of SLE. Participants and methods A case–control study was performed on 50 female patients with SLE (mean age, 32.4 ± 8.6 years) and 50 female healthy volunteers (mean age, 31.9 ± 8.3 years) served as controls. Genotyping was carried out by PCR. The PCR products were digested by NcoI restriction enzyme. Results TNF-α promoter gene polymorphism (rs1800629) GA and AA genotypes and A allele were significantly increased in the studied SLE patients when compared with healthy controls (P = 0.023 and 0.007, respectively). TNF-α genotypes showed significant differences between the various Systemic Lupus Erythematosus Disease Activity Index activity grades (P = 0.012). Moreover, GG genotype had a significantly lower incidence of renal disorders and persistent proteinuria when compared with AG or AA genotypes (P = 0.006 and 0.001, respectively). However, AA genotype showed a significantly higher incidence of neurologic disorders when compared with GG and AG genotypes (P < 0.001 and P = 0.026, respectively). Conclusion Our results indicate that TNF-α (–308 G/A) polymorphism may have a role in the susceptibility and pathogenesis of SLE in the Egyptian population.

Tumor Necrosis Factor-α and Interleukin-1-β Polymorphisms in Pre-Eclampsia.

Pre-eclampsia is the most common critical condition during pregnancy. Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β) increase in pregnant women with pre-eclampsia, compared to normal pregnant women. To investigate the polymorphisms of IL-1β (C+3954T), TNF-α (G-308A), and (G-238A) in pre-eclemptic women in northeastern Iran. This study was conducted on 153 pre-eclamptic women (case group) and 150 healthy pregnant women (control group), admitted to Ghaem and Imam Reza hospitals of Mashhad, Iran. IL-1β (C+3954T), TNF- α (G-238A) and TNF-α (G-308A) gene polymorphisms in the promoter region were screened by polymerase chain reaction. Data were analyzed, using SPSS version 16.0. The mean age of the participants in the case and control groups was 28.2 ± 6.1 and 27.1 ± 6.3 years, respectively (P=0.68). The frequency of G-308A polymorphism was significantly higher in the case group, compared to the control group (p<0.001). However, no significant relationship was found between IL-1β genotype and pre-eclampsia (p=0.39). The frequency of TNF- α (G-238A) AA genotype was significantly higher in the case group, while GG genotype was less frequently detected in the case group, compared to the control group (p<0.001 for both genotypes). Moreover, the frequencies of AA genotypes of -238 TNF-α and G-308A polymorphisms were significantly higher in the case group, compared to the control group (p<0.001). The significant correlation between inflammation promoting genotypes of TNF-α and pre-eclampsia is noteworthy and provides evidence on the contribution of immune related genes in this disease.