TNF2 Allele Research Articles

Single Nucleotide Polymorphisms in Tumor Necrosis Factor-α and Susceptibility to HIV Infection in Local Population of Lahore Pakistan

A single nucleotide polymorphism (SNP) is observed at -308 position of the promoter region of tumor necrosis factor (TNF- α) gene due to which TNF is categorized into TNF1 and TNF2 allele. TNF2 allele is associated with higher concentration of TNF- α which in turn is associated with HIV infection. In order to know the association between TNF2 and HIV infection n =75 HIV positive samples and n=15 HIV negative samples were observed for TNF polymorphism. It was found that among the infected patients 53 patients had TNF2.The total percentage of the patients and controls having TNF2 allele was found to be 63.34.%. Chi square value was significant showing that there is a strong correlation between HIV susceptibility and TNF SNPs (-308) of the promoter region.

The −308 G/A polymorphism in the tumor necrosis factor-α gene is not associated with development and progression of rheumatoid arthritis in Argentinean patients

A polymorphism in the tumor necrosis factor-alpha (TNF-α) promoter region has been associated with disease susceptibility and progression in rheumatoid arthritis (RA). The presence of an adenosine (TNF2 allele) instead of a guanine (TNF1 allele) at position -308 may be responsible for a general increase in the transcriptional activity of the TNF-α gene. Our aim was to evaluate the association of the TNF2 allele with the risk of disease development and/or progression of RA in an Argentine population cohort. Two hundred and twenty-three consecutive patients with RA according to the 1987 criteria of the American College of Rheumatology were included in the study. Clinical variables, Disease Activity Score 28, Health Assessment Questionnaire and Rheumatoid Arthritis Quality of Life were recorded. The radiographic erosions were determined by the method of Sharp/van der Heijde. A group of 111 healthy subjects matched by sex and age was used as a control. All samples were genotyped for the -308 G/A TNF-α polymorphism. No significant differences were observed either in the frequency of the TNF2 allele or in the genotypic distributions of the -308 G/A TNF-α polymorphism (P>0.05) between the control group and the RA patients. No association was found between the TNF2 allele and the variables related to the course and outcome of the disease (P>0.05). In this cohort of Argentinean patients with RA, the TNF2 allele was neither associated with susceptibility to the disease nor was it associated with the variables related to the course and outcome of the disease.

The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (−251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP.ResultsThe TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25–9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease.ConclusionAn analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients.

High plasma TNF-α levels and TNF-α/IL-10 ratios are associated with TNF2 allele in severe P. falciparum malaria patients in Sri Lanka (P3023)

Abstract Plasma levels of pro- and anti-inflammatory cytokines of P. falciparum-infected patients with severe malaria (SM; n=62) and uncomplicated malaria (UM; n=69) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-α (P<0.01), IL-6 (P<0.01) and IL-10 (P<0.05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-α levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n=14) were significantly higher than those of the UM patients (P<0.001) and comparable to SM patients. Plasma IFN-γ levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group whereas percent parasitaemia in all three groups were comparable. Analysis of plasma TNF-α levels and the ratio of TNF-α/IL-10 in UM (n=34) and SM (n=34) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNF-α levels as well as TNF-α/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P<0.05). These results suggest that the high circulating TNF-α levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.

The influence of a TNF gene polymorphism on the severity of rheumatoid arthritis in the Brazilian Amazon

PurposeThe aim of this study was to investigate the influence of the TNF -308 G/A polymorphism in the promoter region of the tumor necrosis factor-α gene on the susceptibility and severity of rheumatoid arthritis (RA) in individuals from the Brazilian Amazon. MethodsA total of 323 individuals—192 healthy controls without arthritis and 131 individuals suffering from arthritis—were genotyped for this polymorphism using a methodology based on PCR-RFLP. ResultsThe frequency of the A allele (TNF2) in rheumatoid arthritis sufferers was not significantly higher than in the controls (p=0.926; OR=0.97; confidence interval 0.54–1.76). However, using a logistic regression model, when the patients were stratified according to whether the manifestations were preponderantly articular or systemic, there was a strong association between the TNF2 allele and systemic arthritis (p=0.001; OR=5.89; confidence interval=1.98–17.5) as well as the use of anti-TNF immunotherapy (p=0.023; OR=1.10; confidence interval=1.00–1.14). The main factors that were found to influence the risk of extra-articular disease were age greater than or equal to 60years (p=0.008; OR=4.06; confidence interval=1.45–11.38), disease duration greater than 10years (p=0.031; OR=3.10; confidence interval=1.11–8.63) and positive rheumatoid factor (p=0.035; OR=2.07; confidence interval=1.05–4.09). ConclusionsThese results suggest that the TNF2 allele is associated with the more serious forms of the disease in individuals from the Brazilian Amazon but not with a risk for developing RA.

Association of high plasma TNF-alpha levels and TNF-alpha/IL-10 ratios with TNF2 allele in severe P. falciparum malaria patients in Sri Lanka

Plasma levels of pro- and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n = 62) and uncomplicated malaria (UM; n = 69) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P<0·01), IL-6 (P<0·01), and IL-10 (P<0·05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n = 14) were significantly higher than those of the UM patients (P<0·001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n = 34) and SM (n = 34) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNF-alpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P<0·05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.

The TNF-α -308 polymorphism may affect the severity of Crohn's disease

OBJECTIVE:The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism.METHODS:This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease.RESULTS:The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03).CONCLUSIONS:The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease.

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women

BackgroundTumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels. MethodsThe G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion. ResultsHomozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15–4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08–4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors. ConclusionsOur results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.

Association of −308G/A polymorphism in the tumor necrosis factor-α gene promoter with susceptibility to development of hantavirus cardiopulmonary syndrome in the Ribeirão Preto region, Brazil

Activation of the immune response in hantavirus cardiopulmonary syndrome (HCPS) leads to a high TNF production, probably contributing to the disease. The polymorphic TNF2 allele (TNF -308G/A) has been associated with increased cytokine production. We investigated the association of the TNF2 allele with the outcome of hantavirus infection in Brazilian patients. A total of 122 hantavirus-exposed individuals (26 presenting HCPS and 96 only hantavirus seroconversion) were studied. The TNF2 allele was more frequently found in HCPS patients than in individuals with positive serology for hantavirus but without a history of HCPS illness, suggesting that the TNF2 allele could represent a risk factor for developing HCPS.

Incidence of adverse cutaneous drug reactions in a Mexican sample: an exploratory study on their association to tumour necrosis factor alpha TNF2 allele

Incidence of adverse cutaneous drug reactions in a Mexican sample: an exploratory study on their association to tumour necrosis factor alpha TNF2 allele

Incidence of adverse cutaneous drug reactions in a Mexican sample: an exploratory study on their association to tumour necrosis factor alpha TNF2 allele

Most adverse cutaneous drug reactions (ACDR) are mediated by delayed hypersensitivity (dh) with lymphocyte recruitment and inflammatory cytokines release, including tumour necrosis factor alpha (TNFalpha). Polymorphisms in the TNFalpha gene, such as the infrequent allele TNF2, predispose to certain inflammatory entities and enhance TNFalpha production. The incidence of the TNF2 allele is increased in British patients with severe ACDR, suggesting TNFalpha as a major contributor in the pathogenesis of ACDR. We designed a prospective study to analyse the epidemiology of ACDR in a third-level Mexican hospital and explore the possibility of a relationship between the TNF2 allele and ACDR-dh. A prospective study during 9 months allowed recognition of 34 ACDR-dh patients. The study included 33 paired patients, and 44 healthy volunteers. All subjects were genotyped for TNF2 by PCR DNA amplification and NcoI restriction endonuclease digestion. Results Incidence of ACDR was 0.95%. The TNF2 allele was detected in 9.9% of the sample population with no significant differences between healthy controls, and patients with or without ACDR-dh. Only 3 of the 34 ACDR-dh subjects presented severe reactions, with 1 having the TNF2 allele. Comorbidity analysis showed significance only with autoimmune thyroid disease, consistent with reports on Chinese and Tunisian patients. ACDR incidence and TNF2/TNFA heterozygosity were lower in Mexican than in Caucasian patients. ACDR-dh patients showed no increased frequency in the TNF2 allele.

Effect of the Polymorphism of Tumor Necrosis Factor-α-308 G/A Gene Promoter on the Susceptibility to Ulcerative Colitis: A Meta-Analysis

Background: Ulcerative colitis (UC) is a complex polygenic disease in which gene-environment interactions are important. Some studies have reported that proinflammatory polymorphisms in tumor necrosis factor-α-308 (TNF-α-308) gene promoter (substitution G→A, designated as TNF1 and TNF2) is associated with increased UC risk. However, the results of individual studies have been inconsistent. Methods: To investigate the inconsistent findings in studies of the association of the polymorphism of TNF-α-308 gene promoter with susceptibility to UC, a systematic review of the published data was undertaken and a meta-analysis was performed. The MEDLINE database was searched for case-control studies published in English language journals from 1966 to November 2007. Data were extracted using standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: 15 eligible studies, 7 of Europeans, 2 of Americans, and 6 of Asians including 4 East Asians, were included in the meta-analysis. An association between UC and TNF2 allele was not found in the overall population (OR 1.28, 95% CI 0.84–1.96, p = 0.25). However, stratification by ethnicity indicated that there was significant association between TNF2 allele and UC in East Asians (OR 2.27, 95% CI 1.08–4.77, p = 0.03). Conversely, there was no association between TNF2 allele and UC patients from the European (OR 0.85, 95% CI 0.42–1.71, p = 0.65) and Asian samples (OR 1.64, 95% CI 0.98–2.74, p = 0.06). The OR for the TNF2/2+TNF2/1 genotype versus TNF1/1 genotype in samples overall and in each ethnic group showed a similar trend to those for the TNF2 allele. Conclusion: In East Asians, the TNF2 allele confers a significant risk for developing UC. There is no association between the polymorphism of TNF-α-308 gene promoter and UC in Europeans.

Polymorphisms of TNF-alpha and LT-alpha genes in multiple myeloma

Allelic distribution of −308 G > A ( TNF 1/2) polymorphism of the TNF-alpha, and the +252 A > G promoter polymorphism of the LT-alpha gene, the 1267 A > G polymorphism of the HSP70-2 gene as well as the −429 T > C promoter polymorphism of the RAGE gene were tested in 94 MM cases and 141 controls. Significantly less MM patients than controls carried the TNF2 allele ( p = 0.018) and the TNF2-LTA 252G haplotype ( p = 0.025). The difference was, however, restricted to the females, as well as the relatively young (<69 years) subjects. By contrast, we did not find differences with the other SNPs tested.

Human leucocyte antigen and TNFα polymorphism association in microscopic colitis

Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.

TNFα in patients with end-stage heart failure on medical therapy or supported by a left ventricular assist device

Background In the heart elevated levels of TNFα can cause lethal heart failure, like Dilated Cardiomyopathy (DCM). The level of TNFα production is in part determined by promoter gene polymorphisms. We investigated whether the TNFα promoter gene polymorphism is in this way involved in the outcome of end-stage heart failure and predicts whether patients require left ventricular assist device (LVAD) support or can be kept on medical therapy (MT)while awaiting heart transplantation (HTx). As most patients in this study received a heart transplant, the role of the TNFα polymorphisms in transplant rejection was studied as well. Methods and results In twenty nine patients with DCM, 35 patients with Ischemic Heart Disease (IHD; both on MT), 26 patients on LVAD support and 61 cardiac transplant donors TNFα plasma level was detected by EASIA. In both patients groups high levels of TNFα plasma levels was observed however, in patients supported by LVAD this increase was much higher compared to patients on MT. Furthermore, this increase seems to be associated with the TNF 1 allele (‘G’ at position − 308) instead of the TNF2 allele (A at position − 308). The promoter polymorphisms at positions − 238, − 244 and − 308 were observed by polymerase chain reaction and sequencing. Polymorphism at positions − 238, − 244 and − 308 did not show any relevant differences between the groups. However, at position − 308, a trend of a higher incidence of the TNF2 allele (an “A” at position − 308) in DCM patients compared to donors was shown. The distribution of the TNF1 and TNF2 alleles was not different in patients on medical therapy compared to the patients supported by a LVAD. No association was found between patients' TNFα promoter gene polymorphism and rejection. However, patients that received a donor heart with the TNF2 allele developed more rejection episodes, compared to patients that received a donor heart with the TNF1 allele. Conclusion TNFα levels are high in patients with end-stage heart failure on MT, but even higher in patients on LVAD support. These high TNFα plasma levels however, are not correlated with the TNF2 allele but seems to be associated with the TNF1 allele. Furthermore, in HTx the donor TNFα gene seem to play a more important role in severity of acute rejection than that of the patient.

The association between polymorphism of TNF-α gene and hypertensive disorder complicating pregnancy

To study whether the development of hypertensive disorder complicating pregnancy is associated with -308G-->A, -850C-->T mutation at promoter of TNF-alpha gene, the -308G-->A, -850C-->T polymorphism was examined in patients and healthy pregnant women by PCR-RFLP technique. The frequencies of genotype and allele were compared between the two groups. The results showed that with -308G-->A polymorphism distribution, the allele frequency of TNF2 and the frequency of the genotype TNF2/1 in the patient group was significantly higher in the patient group than in control group (P<0.05). A significant difference in genotype distribution of -850C-->T polymorphism was observed between the two groups. The allele frequencies of T in patient group was higher in the control group as compared with the patient group. The frequencies of CT and TT genotypes were lower in the patient group. It is concluded that the TNF2 allele of -308 is associated with the occurrence of hypertensive disorder complicating pregnancy, while T allele of -850 may be the protective factor against the development of the disease. TNF2/1 CC may be susceptibility genotype of hypertensive disorder complicating pregnancy.

Polymorphisms in the tumor necrosis factor-alpha gene in Turkish women with pre-eclampsia and eclampsia.

The genetic background predisposing pregnant women to pre-eclampsia/eclampsia (PE/E) is still unknown. The aim of the current study was to investigate whether there is an association between the TNF-alpha-308 and 850 polymorphisms and PE or eclampsia. In this study, 40 cases of eclampsia, 113 cases of PE and 80 normotensive control cases were genotyped for the TNF-alpha-G-308A and C-850 polymorphisms. At position 308, the replacement of Guanine with Adenosine was denoted as TNF2. We found a significant difference between the TNF2 allele frequencies of the eclamptic, pre-eclamptic and normotensive controls. TNF2 (AA) polymorphism frequency was significantly higher among the eclamptics and pre-eclamptics (control : 5%, PE : 13.3%, E : 12.9%). A significantly different genotype distribution of C-850T polymorphism was observed between the PE/E and control groups, with the frequency of the variant TT genotype being significantly reduced in the preeclamptics (PE : 17% ; E : 17.5%) when compared with the control group (24.3%). We have demonstrated an association between TNF-alpha polymorphisms and pre-eclampsia susceptibility. However, it is not known whether C-850T polymorphism has a functional effect on the TNF-alpha gene. In addition, it was not possible to determine whether this polymorphism promotes the progression from PE to eclampsia because of no statistically significant difference between eclampsia and the controls.

Tumor Necrosis Factor-α-308 Gene Polymorphism in Croatian and Slovenian Multiple Sclerosis Patients

Previous findings regarding the role of TNF-α-308 gene polymorphism in multiple sclerosis (MS) are contradictory. The aim of this study was to investigate the possible influence of TNF-α-308 polymorphism on MS susceptibility and the MS disease process in a Croatian and Slovenian population. Genotyping was performed in 338 patients and 460 healthy controls. The TNF2 allele was present in 123 (26.8%) healthy controls vs. 67 (19.9%) MS patients (p = 0.023, odds ratio = 0.68, 95% confidence interval = 0.48–0.95), suggesting that carriage of the TNF2 allele might decrease MS risk. The difference in TNF2 allele carrier frequency between patients and controls was identified in the relapsing-remitting MS group. There was no association between TNF2 allele carrier status and age at disease onset or disease progression. Our results suggest that, in the study populations, the TNF-α-308 polymorphism may play a role in MS susceptibility.

Genetically determined imbalance between serum levels of tumour necrosis factor (TNF) and interleukin (IL)-10 is associated with anti-Jo-1 and anti-Ro52 autoantibodies in patients with poly- and dermatomyositis

Our aim was to investigate presence of tumour necrosis factor (TNF) and interleukin (IL)-10 in serum and their relation to different genotypes as well as to clinical and laboratory phenotypes in patients with polymyositis and dermatomyositis. In 65 patients with poly- or dermatomyositis the inflammatory cytokine balance was evaluated by the assessing absolute levels as well as the ratio between TNF and IL-10 in serum. These levels were correlated to the G-308A TNFA, G-1087A IL10 and G915C TGFB1 gene polymorphisms and haplotype frequencies, gender, autoantibody profiles and clinical manifestations. Increased serum levels of TNF and IL-10 were observed in patients compared to controls. A significantly higher TNF:IL-10 ratio was detected in female poly- and dermatomyositis patients carrying the TNF2 allele compared to female patients with the TNF1/TNF1 genotype (median ± IQR 1.513 ± 0.0.679 vs. 0.950 ± 1.173, p = 0.021). This ratio was also significantly higher in patients with the extended MICA5.1/TNF2/TNFa2/DRB1*03 haplotype compared to patients lacking this haplotype. A significantly higher TNF:IL-10 ratio was recorded in sera of patients with anti-Ro52 (1.513 ± 1.275 and 1.276 ± 0.671, positive vs. negative, p = 0.010) antibodies and in women with anti-Jo-1 (1.919 ± 0.918 and 1.281 ± 0.790, positive vs. negative, p = 0.041). Our data suggest that a genetically programmed cytokine imbalance exists in patients with poly- or dermatomyositis and that this imbalance is related to the presence of disease-associated autoantibodies.

Impact of genetic variation of tumor necrosis factor-α on gestational hypertension

The mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory Th(1)-type cytokine. TNFA gene is located in the human leukocyte antigen (HLA) class III region of the major histocompatibility complex (MHC) on chromosome 6. The high TNF-alpha mRNA expression may be associated with the TNF2 (A) allele, which is the polymorphism of TNF-alpha at position -308 in promoter region. This study assessed whether the TNF2 (A) allele at position -308 plays a role in the alteration of blood pressure (BP) and urinary protein excretion during pregnancy. The original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism (RFLP) analysis with Nco I enzyme. The distributions of the G/A polymorphism of TNF-alpha in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 (A) allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure (P > 0.05). The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 (A) allele compared to homozygous for the TNF1 (G) allele (systolic BP, P < 0.01 and diastolic BP, P < 0.05). The elevated blood pressure in the TNF2 (A) group was accompanied by higher urinary protein excretion in the third trimester (P < 0.05). The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters (P > 0.05). Maternal TNF2 (A) allele of TNF-alpha promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.