Tumor Necrosis Factor-alpha Polymorphisms Research Articles

Determination of the Gene Polymorphisms of Tumor Necrosis Factor-Alpha and Interleukin-10 in Coronary Artery Disease Patients in Iraq

Determination of the Gene Polymorphisms of Tumor Necrosis Factor-Alpha and Interleukin-10 in Coronary Artery Disease Patients in Iraq

A case-control study of tumor necrosis factor-alpha promoter polymorphism and its serum levels in patients with chronic obstructive pulmonary disease in Kashmir, North India.

Aim:Data about polymorphism in tumor necrosis factor-alpha (TNF-α) and its serum levels in chronic obstructive pulmonary disease (COPD) are conflicting. We aimed to evaluate the association of TNF-α-308 G > A polymorphism in patients with COPD in Kashmir (North India), a high burden area and also determined the serum TNF-α levels in these patients.Materials and Methods:One hundred spirometrically confirmed COPD patients and 163 controls resident from Kashmir valley (North India) were recruited. Genotyping of the promoter region of TNF-α was carried out using polymerase chain reaction-restriction fragment length polymorphism. The serum TNF-α was quantified using the Cytometric Bead Array flex system by flow cytometry. Results were subjected to appropriate statistical treatment and P < 0.05 was considered statistically significant.Results:Ninety-one COPD patients (91%) had G/G (wild homozygous) genotype and nine patients (9%) had G/A (heterozygous) genotype. Among the control population, 150 (92%) had G/G genotype and 13 (8%) had G/A genotype. The variant allele “A” was not detected in either of the two groups. Serum levels of TNF-α were significantly higher in patients compared to control group (8.0 ± 10.1 pg/ml vs. 3.3 ± 0.42 pg/ml, respectively, P = 0.0001).Conclusion:While serum levels of TNF-α are higher in COPD patients compared to the controls, there was no difference in the prevalence of TNF-α-308 polymorphism in the ethnic Kashmiri population with COPD.

Tumor Necrosis Factor-Alpha Polymorphisms in the Pathogenesis of Chronic Spontaneous Urticaria.

Tumor Necrosis Factor-Alpha Polymorphisms in the Pathogenesis of Chronic Spontaneous Urticaria.

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.

Association between interleukin-1, interleukin-6, and tumor necrosis factor-alpha polymorphisms and juvenile idiopathic arthritis: a meta-analysis

In juvenile idiopathic arthritis (JIA), interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are associated with development and progression of JIA. We investigated whether IL-1, IL-6, and TNF-α polymorphisms were associated with susceptibility to JIA. A meta-analysis was conducted on the associations between IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA (PubMed and Embase). A total of 27 studies involving 4678 JIA patients and 7634 controls were considered in the meta-analysis. There was no association between the IL-1α-899 C/T, IL-1β-511 C/T, IL-6-174 G/C, and TNF-α-308 G/A and -238 G/A polymorphisms, and JIA in allele contrast or any other genetic models. In subgroup analysis based on subtype, except for the dominant model of TNF-α-238 G/A, systemic JIA was not significantly associated with IL-6 and TNF-α polymorphisms. In Caucasians, the dominant and additive models of IL-1β-511 C/T were significantly associated with JIA (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.09-2.00, P=0.01; OR 1.46, 95% CI 1.05-2.03, P=0.02, respectively). This meta-analysis showed no association between IL-1, IL-6, and TNF-α polymorphisms, and JIA, but the TT genotype of IL-1β -511 C/T was associated with higher prevalence of JIA in Caucasians.

Association of rs1800629 tumor necrosis factor alpha polymorphism with risk of prostate tumors of Iraqi patients

Several factors associated with prostate cancer, one of them is inflammation. Tumor necrosis factor alpha (TNF-α) cytokine has an important role in inflammation. The aim of this study was to investigate the effect of TNF-α-308 (G/A) polymorphism on the potential danger of prostate tumors on Iraqi prostate tumors patients. In this research, the gene polymorphism of TNF-α in sixty patients, thirty of which were diagnosed with prostate cancer(PCa) and thirty with benign prostate hyperplasia (BPH), and also in thirty healthy volunteers serving as the control group was studied. Specific primers were used for the amplification of the promoter region of TNF-α (rs1800629) by Polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) was used for the determination of the alleles frequencies associated with each group of the study subjects. The result of RFLP showed that GA allele was correlated with both BPH and PCa, leading to a conclusion that GA allele in TNF-α gene polymorphism may be considered a risk factor for developing PCa.

The effect of tumor necrosis factor alpha (-308G/a) and interferon gamma (+874T/a) polymorphisms on susceptibility to coronary heart disease

Background: Coronary heart disease (CHD) is a chronic inflammatory disease, which is still regarded as a major cause of morbidity and mortality worldwide. Several studies have suggested that polymorphisms in cytokine genes are associated with the pathogenesis of CHD. The genotype distribution of Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) genes polymorphisms have been shown to be different in various ethnic populations. This study was aimed to investigate the association of TNF-α-308 G/A and IFN-γ + 874T/A polymorphisms with risk of CHD in an Iranian population.Methods: A total of 187 unrelated subjects comprised 96 CHD patients and 91 healthy controls were enrolled in this cross-sectional study. The TNF-α-308 G/A and IFN-γ + 874T/A polymorphisms were genotyped using amplification refractory mutation system-PCR (ARMS-PCR). The chi-square and logistic regression tests were used to calculate the odds ratios (ORs) as a measure of differences in genotype frequencies.Results: A significant differences in the allelic and genotypic distribution of TNF-α-308 G/A and IFN-γ + 874T/A polymorphisms was found between CHD patients and healthy controls (P = 0.017, P = 0.011, P = 0.006 and P = 0.002, respectively). Logistic regression analyses were also revealed statistically significant risk for CHD with respect to TNF-α-308 A and IFN-γ + 874 T carriers either in crude or after adjustment for potential confounders (P = 0.003 and P = 0.006, respectively).Conclusion: This study provides strong evidence supporting the association of TNF-α-308G/A and IFN-γ + 874T/A polymorphisms with the increased risk of CHD. Therefore, these two cytokine polymorphisms may play a role in predisposition to coronary heart disease.

Association between tumor necrosis factor alpha gene polymorphisms and multiple myeloma risk: an updated meta-analysis

ABSTRACTObjectiveThis study aimed to investigate the relationship between tumor necrosis factor alpha (TNFα) polymorphisms and multiple myeloma (MM) risk.MethodsEligible studies were retrieved from PubMed, the Cochrane Library, Embase, CNKI and the Wanfang database. Polymorphisms of TNFα-308 G/A, TNFα-857 C/T, and TNFα-238 G/A were analyzed based on the allele, recessive, dominant, and additive-dominant models. The meta-analysis was conducted using R 3.12 software. Odds ratio (OR) and 95% confidence intervals (CI) were used as evaluation indicators. Heterogeneity among studies was detected. Publication bias was evaluated. Sensitivity and power analyses were also conducted.ResultsSignificant associations existed between ‘TT vs. CC’ (OR = 2.3752, 95% CI = 1.1342–4.9740) and ‘TT vs. CC + TC’ (OR = 2.0802, 95% CI = 1.0250–4.2218) models of the TNFα-857 C/T gene and MM risk. There were no significant differences in other genetic models of TNFα-857 C/T or any genetic models of TNFα-308 G/A and TNFα-238 G/A. No significant publication bias existed among the studies. In addition, sensitivity analyses showed that meta-analysis results of all genetic models of the TNFα-238 G/A gene did not change after omitting one of these studies, but most models of TNFα-857 C/T and TNFα-308 G/A exhibited significant changes.ConclusionOur findings indicate that the ‘TT vs. CC’ and ‘TT vs. CC + TC’ of TNFα-857 C/T are correlated with MM risk. TNFα-857 C/T may be a risk factor for MM development. There is no association between TNFα-238/-308 polymorphisms and MM risk.

342. Association between Tumor Necrosis Factor Alpha (TNF-α) polymorphisms and haplotypes and preeclampsia risk

Introduction Preeclampsia is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Excessive release of pro-inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-α) has been demonstrated to contribute to endothelial activation and default of trophoblasts invasion that result in the clinical symptoms of preeclampsia. Genetic polymorphisms of TNF-α could regulate its production and may play an important role in the pathogenesis of this disease. Objective/hypothesis The aim of this study was to evaluate the association of five different TNF-α gene promoter single nucleotide polymorphisms (SNPs), or their haplotype combinations, with the development of preeclampsia. Methods This a case-control study conducted on 300 women with PE and 300 age-matched women with normal pregnancy from Tunisian hospitals. Genotyping of TNF-α −1031T/C, −376G/A, −308G/A, −238G/A, and + 488C/T SNPs was performed on DNA extracted from blood samples. TNF-α genotyping was assessed using PCR-restriction fragment-length polymorphism (RFLP) analysis. Statistical analysis was performed using the chi-square test. P values less than 0.01 were considered statistically significant. Results Our results demonstrated a higher frequency of the minor allele − 1031C (p ⧹ A is associated with lower systolic blood pressure while the minor allele is associated with increased diastolic blood pressure. Discussion These results demonstrate that TNF-α polymorphisms, in particular − 1031C/A and − 376 G/A, are significantly associated with preeclampsia. In addition, we found a protective effect of the major allele G of − 308 G ⧹ A SNP on systolic blood pressure while increased diastolic blood pressure can be found in carriers of the minor allele A.

Correction to: Assessment of tumor necrosis factor alpha polymorphism TNF-α−238 (rs 361525) as a risk factor for development of acute kidney injury in critically ill patients

The title of the original article has been corrected to: Assessment of tumor necrosis factor alpha polymorphism TNF-α-238 (rs 361525) as a risk factor for development of acute kidney injury in critically ill patients. The original article has been corrected to reflect the correct title.

Assessment of tumor necrosis factor alpha polymorphism TNF-α-238 (rs 361525) as a risk factor for development of acute kidney injury in critically ill patients.

this study evaluated the association of TNF-a-238 (rs 361525) with adverse outcomes in critically ill patients. TNF-α-238 (rs 361525) SNP was performed by RT-PCR on 200 critically-ill patients (112 had severe sepsis and septic shock and 88 were septic), 127 of them had AKI. Urinary N-acetyl-β-(D)-glucosaminidase and serum creatinine were assessed by modified Jaffé and ELISA respectively. These results revealed that heterozygous genotype GA of TNF-α-238 (rs 361525) SNP significantly increased the risk of adverse-outcome (mortality rate) (P = 0.0001; OR 8.9), regardless of organ dysfunction (P = 0.09) or severity of sepsis (P = 0.6). Moreover, heterozygous genotype GA of TNF-α-238 (rs 361525) SNP was significantly associated with inflammatory marker (sTNF-α) (P = 0.014) and tubular injury marker (uNAG) (P = 0.001) that displayed a significant association with severity of sepsis (0.001, 0.035) and organ dysfunction (0.012, 0.0001) respectively. In critically ill patients with sepsis induced AKI, serum TNF-α and uNAG measured at admission can predict severity of sepsis and AKI (defined by REFILE) occurrence along with pre-existing CKD and DM. However, TNF-238 yielded additional prognostic information on ICU mortality irrelevant to AKI in septic patients.

Tumor Necrosis Factor-Alpha (TNF-α-308 G>A) Polymorphism in High-grade Gliomas.

High-grade gliomas (HGG) consist of anaplastic oligoastrocytomas, anaplastic oligodendrogliomas, anaplastic astrocytomas and glioblastoma multiforme. The present study aimed to evaluate TNF-α -308 G>A polymorphism in a Turkish population. This was a prospective case-control study that included 45 patients with HGG and 49 healthy individuals. All patients were operated for intracranial tumors and the pathology results consist of high grade (Grade3 and 4) glial tumors. No significant differences were found between the HGG and control groups in terms of the median age (p=0.898). There were no significant differences with regard to gender (p=0.577). The TNF genotype frequency comparison between patients and controls was not statistically significant (p=0.598). TNF genotype frequency comparison between the patients and controls was not statistically significant in the Turkish population tested. However, further studies are needed to evaluate the genotype and phenotype correlations in large cohorts of various ethnicities.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

Background:The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha.Aims:To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels.Study Design:Case-control study.Methods:Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction–restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay.Results:We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05).Conclusion:Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Tumor necrosis factor alpha polymorphisms are associated with Parkinson's disease age at onset.

The role of neuroinflammation in Parkinson's disease (PD) has been demonstrated through several different approaches. It was suggested an inflammation-derived oxidative stress and cytokine-dependent toxicity role in the nigrostriatal pathway degeneration and hasten progression of disease. Tumor necrosis factor alpha (TNFA) gene promoter polymorphisms might alter the expression of this cytokine contributing to the pro- and anti-inflammatory polarization. An increased TNFA expression might lead to inflammatory profile predominance. The aim of study was to determine if TNFA haplotypes are associated with PD age at onset. Five polymorphisms in TNFA gene were investigated in 226 patients with idiopathic PD in relation to age at onset. Haplotype grouping was based on allele expression. Logistic binary regression analysis showed that the genetic background leading to higher TNF-α expression confers a higher risk to develop PD earlier. Gender and ancestry did not differ between groups. High TNFA expression may contribute for faster dopaminergic neuron degeneration. In this context, a higher genetic pro-inflammatory profile confers a higher risk to develop PD earlier.

Meta-Analysis of the Relationship between TNF-α (−308G/A) and IL-10 (−819C/T) Gene Polymorphisms and Susceptibility to Dengue

ABSTRACTObjective: This study determined whether tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10) polymorphisms are associated with susceptibility to dengue.Methods: a systematic review with meta-analysis was conducted of the associations between the TNF-α (−308G/A) and IL-10 (−819C/T) polymorphisms and dengue.Results: A total of eight case-controls studies involving 384 individuals with symptomatic dengue, 571 individuals with dengue hemorrhagic fever, and 995 healthy controls were considered in the meta-analysis. There was no significant association between TNF-α (−308G/A) and IL-10 (−819C/T) polymorphism and dengue in overall population. However, stratifying meta-analysis by groups, the meta-analysis revealed association between the TNF-α −308 G/G (OR: 1.62, CI: 1.02–2.57, p = 0.04) genotype and allele G (OR: 1.62, CI: 1.04–2.55, p = 0.03) that confers susceptibility to symptomatic dengue, while the TNF-α −308 G/A genotype (OR: 0.69, CI = 0.39–0.99, p = 0.04) and allele A (OR: 0.64, CI: 0.41–1.00, p = 0.05) confers protection to symptomatic dengue. No difference was observed for the TNF-α (−308) and IL-10 (−819C/T) polymorphisms in the comparisons of hemorrhagic dengue versus control and hemorrhagic dengue versus symptomatic dengue.Conclusion: This meta-analysis showed that TNF-α (−308) polymorphism is associated with dengue symptomatic susceptibility.

Tumor Necrosis Factor Alpha Gene Polymorphism and Association With Its Serum Level in Iranian Population with Rheumatoid Arthritis.

This study aims to determine whether promoter -238 G/A polymorphism in tumor necrosis factor-alpha (TNF-α) gene is associated with susceptibility to rheumatoid arthritis (RA) in Iranian population and serum level of TNF-a. This case-controlled study was performed on two groups including 90 RA patients (20 males, 70 females; mean age 50.3 years; range 26 to 65 years) and 90 healthy controls (21 males, 69 females; mean age 48.6 years; range 27 to 63 years). We determined the frequency of -238 G/A TNF-a gene polymorphism by polymerase chain reaction restriction fragment length polymorphism. We measured the serum level of TNF-a using enzyme-linked immunosorbent assay method. Also, we determined the association of serum TNF-a level with the polymorphism in RA patients. There was no significant difference in terms of sex and age in the two groups. In the RA group, the genotype frequency of -238 G/A polymorphism was GG (76.6%), GA (17.8%), and AA (5.6%). In the control group, the genotype frequency of -238 G/A polymorphism was GG (83.5%), GA (8.8%), and AA (7.7%). Statistical analysis showed no significant difference in the genotype frequency of this polymorphism between two groups (p=0.07). The serum level of TNF-a were 5.21±1.69 Pg/mL (range 0 to 11.6) in the control group and 62.4±27.1 Pg/mL (range 0 to 117.22) in the RA group (p<0.0001). There was no significant difference in terms of serum TNF-a level and different genotypes in the RA group (p=0.5). Our findings demonstrate that the TNF-a -238 G/A gene polymorphism may not represent a significant risk factor for RA in Iranian population and there is no association between the polymorphism and serum TNF-a level in RA patients.

Three polymorphisms of tumor necrosis factor-alpha and hepatitis B virus related hepatocellular carcinoma: A meta-analysis.

To assess the association between tumor necrosis factor-alpha (TNF-α) G308A, G238A and C863T polymorphisms and hepatitis B virus related hepatocellular carcinoma (HBV-HCC) susceptibility. We interrogated the databases of Pubmed, Sciencedirect and Viley online library up to March 8, 2016. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated in a fixed-effects model or a random-effects model when appropriate. In total, 12 case-control studies which containing 1580 HBV-HCC cases, 2033 HBV carrier controls, 395 HBV spontaneously recovered (SR) controls and 1116 healthy controls were included. Compared with GG genotype, the genotypes GA/AA of G308A were associated with a significantly increased HBV-HCC risk when the controls were all healthy individuals (AA vs. GG, OR 2.483, 95%CI 1.243 to 4.959; GA vs. GG, OR 1.383, 95%CI 1.028 to 1.860; GA/AA vs. GG, OR 1.381, 95%CI 1.048 to 1.820). Meanwhile, only the AA vs. GG model of G238A and HBV-HCC showed a statistic significance when the controls were healthy individuals (OR 4.776, 95%CI 1.280 to 17.819). CT genotype of TNF-α C863T could increase HBV-HCC risk whenever the controls were healthy individuals, HBV carriers or HBV recovers. This meta-analysis shows that AA genotype in TNF-α G308A and TNF-α G238A and CT genotype in TNF-α C863T may increase HBV-HCC risk. Therefore, HBV infection seemed to be a more important factor for tumorigenesis of HCC than genetic predisposition in G308A of TNF-α, and interaction between TNF-α C863T polymorphisms and HBV infection might be associated with increased HCC risk.

Association of TNF-α -308G>A and TNF-β +252A>G genes polymorphisms with primary immune thrombocytopenia: a North Indian study.

Primary immune thrombocytopenia (ITP) is manifested by platelet autoantibodies that are not only responsible for platelet destruction by phagocytosis but also inhibit their production. Bleeding is the most common clinical manifestation of thrombocytopenia. ITP is a multifactorial disease in which both environmental and genetic factors have been implicated. It has been reported that several gene polymorphisms influence host susceptibility to ITP. This study was aimed to investigate the association of polymorphisms in tumor necrosis factor-alpha (TNF-α) 308 G>A and TNF-β +252 A>G genes with primary ITP in Indian patients. Genotyping for the TNF-α -308 G>A and TNF-β +252 A>G was performed in 80 ITP patients and 100 controls by polymerase chain reaction and restriction fragment length polymorphism. We found no significant difference in distribution of TNF-α heterozygous variant genotype (GA) among patients and controls. Homozygous variant genotype (AA) was absent both in patients and controls. No statistical difference was observed in the distribution of heterozygous variant (AG) and homozygous variant (GG) genotypes of TNF-β, between patients and controls. Heterozygous (AG) genotype of TNF-β -308G>A was associated with persistent ITP. The study showed that heterozygous variant (AG) genotype of TNF-β was associated with persistent ITP, when compared with controls. We could not find any association of TNF-α with susceptibility in developing ITP. Furthermore, no association was observed with respect to different categories of ITP. In addition, additive model showed two-fold increased susceptibility to ITP. We conclude that single nucleotide polymorphism in TNF-β +252 A>G gene may have impact on susceptibility to ITP.

Polymorphisms in tumor necrosis factor-alpha (−863C>A, −857C>T and +488G>A) are associated with idiopathic recurrent pregnancy loss in Korean women

Polymorphisms in TNF-a have been reported as genetic risk factors for recurrent spontaneous abortion and TNF-α may be immunologically important. We therefore examined the contribution of several TNF-a mutations to this phenomenon. The study participants consisted of 388 patients with idiopathic recurrent pregnancy loss (RPL), which was diagnosed on the basis of at least two consecutive spontaneous abortions; control subjects were 224 healthy women with a history of successful pregnancies. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to determine the TNF-α −863C>A, −857C>T, and +488G>A genotypes. The TNF-α −863C>A variants correlated with increased risk of RPL (CA+AA; adjusted odds ratio [AOR], 2.142; 95% confidence interval [CI], 1.493–3.074). These data did not differ in a stratified analysis according to number of consecutive spontaneous abortions. In haplotype analysis, there were similar trends of data for combination analysis, but in patients with 3+ pregnancy losses, a stratified analysis revealed that this correlation did not increase directly with the number of pregnancy losses. The TNF-α −863C>A variant is a possible genetic risk factor for idiopathic RPL in Korean women.

Association of TNF-α genetic polymorphisms with recurrent pregnancy loss risk: a systematic review and meta-analysis

BackgroundSeveral studies on the association of tumor necrosis factor alpha (TNF-α) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-α polymorphisms and RPL.MethodsAn extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software.Results10 case–control studies including 1430 RPL patients and 1727 healthy controls were identified. Meta-analysis indicated that TNF-α-308G/A (rs1800629) polymorphism in the TNF-α gene correlated with elevated RPL risk whereas no significant association was observed between TNF-α-238G/A (rs361625) and RPL.ConclusionsThe current meta-analysis demonstrates that TNF-α-308G/A polymorphism in the TNF-α gene is associated with susceptibility to RPL.