Tumor necrosis factor-α promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE) (original) (raw)
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Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients
Human Immunology, 2017
The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (-308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α-308A (OR = 2.3, p = 0.0001, Pc = 0.0003) and LTα+252G (OR = 2.1, p < 0.0001, Pc < 0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR = 12.2, p = 0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles.
Human Immunology, 2004
Tumor necrosis factor (TNF) is involved in the pathogenesis of systemic lupus erythematosus (SLE), but the role of TNF polymorphisms in SLE susceptibility remains unclear. Previous studies in different populations report an inconsistent association of the TNF-␣ Ϫ308A allele with SLE, sometimes depending on the presence of HLA-DR3. We examined the association of polymorphisms in TNF-␣ (Ϫ308G/A, Ϫ238G/A) and TNF (ϩ252A/G) in a population-based study of SLE in the southeastern United States and considered TNF-SLE associations with respect to HLA-DR3 and DR2 and the interleukin (IL)-1␣ Ϫ889C/T polymorphism, previously linked to SLE in this population. Genotypes were analyzed for 230 recently diagnosed SLE patients who met American College of Rheumatology classification criteria and 276 age-and sex-matched controls, randomly selected from driver's license registries. Carriage of the TNF-␣
A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha
European Journal of Immunology, 1994
We have investigated the significance of tumor necrosis factor alpha (TNF-a) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production.Typing of HLA-B, -DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti-Ro and anti-La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6],asdidHLA-DR3(0.25vs. 0 . 1 3 ,~ < 0.01, OR = 2.3)andHL,A-B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA-DR3 showed the strongest disease association, we could not demonstrate association of HLA-DR3 or TNF2 with SLE independently of each other.Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti-Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti-La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA-DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8-DR3 haplotype,TNF-a polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.
Indian Journal of Clinical Biochemistry, 2019
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease which is characterized by dysregulation of various cytokines propagating the inflammatory processes that is responsible for tissue damage. Tumor necrosis factor alpha (TNF-a) is one of the most important immunoregulatory cytokines that has been implicated in the different autoimmune diseases including SLE. Two hundred and two patients with SLE and 318 controls were included in the study. The TNF-a gene promoter region (from-250 to-1000 base pairs) was analyzed by direct Sanger's DNA sequencing method to find promoter variants associated with South Indian SLE patients. We have analyzed six TNF-a genetic polymorphisms including,-863C/A (rs1800630),-857C/T (rs1799724),-806C/T (rs4248158),-646G/A (rs4248160),-572A/C (rs4248161) and-308G/A (rs1800629) in both SLE patients and controls. We did not find association of TNF-a gene promoter SNPs with SLE patients. However, the-863A (rs1800630) allele showed association with lupus nephritis phenotype in patients with SLE (OR: 1.62, 95%CI 1.04-2.53, P = 0.034). We found serum TNF-a level was significantly elevated in SLE cases as compared to control and found no association with any of the polymorphisms. The haplotype analysis revealed a significant protective association between the wild TNF-a alleles at positions-863C,-857C,-806C,-646G,-572A and-308G (CCCGAG) haplotype with lupus nephritis phenotype (OR 0.53, 95% CI 0.35-0.82, P = 0.004). Additionally, the TNF-a-863 C/A (rs1800630) polymorphism and HLA-DRB1*07 haplotype showed significant differences between SLE patients and controls (OR 4.79, 95% CI 1.73-13.29, P = 0.0009). In conclusion, TNF-a-863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-a-863 C/A promoter polymorphism giving supportive evidence for the tight linkage disequilibrium between TNF-a promoter SNPs and MHC class II DRB1 alleles. Keywords Autoimmune disease Á Auto antibodies Á Systemic lupus erythematosus Á Cytokine Á Tumor necrosis factor alpha Á Major histocompatibility complex Á Human leukocyte antigen Á Inflammation
International Journal of Immunogenetics, 2007
The production of cytokine varies among individuals and correlates with the polymorphism of cytokine genes. Three functional single nucleotide polymorphisms (SNPs) at position-863,-308, and-238 in the tumour necrosis factor alpha (TNF-α) gene promoter were analysed for association with systemic lupus erythematosus (SLE) (n = 154), and clinical manifestations in a Thai population were compared with 154 ethnically matched controls. The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism method. The association between these SNPs and SLE was analysed using chi-squared test. The-863A allele and-863A,-308G,-238G haplotype were found to be significantly increased in SLE patients (25%) compared with healthy controls (15.3%) (Pc = 0.009, OR = 1.85, 95% CI = 1.21-2.83). In addition-863A allele was found to be significantly increased in the SLE group with Raynaud's phenomenon compared to SLE without Raynaud's phenomenon (35% vs. 19.4%) (Pc = 0.048, OR = 2.23, 95% CI = 1.21-4.10). The-863A allele of TNF-α gene and the extended haplotype of-863A,-308G,-238G can be used as a genetic marker for SLE susceptibility in Thai populations. In addition, the-863A genotype could produce high TNF levels and potentially induce the occurrence of Raynaud's phenomenon.
2012
The polymorphism of the tumor necrosis factor (TNF) promoter gene at position -308 and that of the lymphotoxin alpha (LTA) gene at position 252 have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. In a nested case-control study, we investigated the possible association of these polymorphisms with susceptibility to SLE and with phenotypic disease features in Portuguese Caucasian patients. TNF-308 G>A and LTA 252 A>G polymorphisms were determined by restriction fragment length polymorphism analysis in a cohort of 115 SLE patients and 152 unrelated healthy controls, and the magnitude of the association between genotypes and SLE diagnosis was calculated. For SLE patients, we also tested the association between disease characteristics and genotypes. No significant differences in genotype or allele frequencies could be identified between SLE cases and controls. Lupus nephritis (OR = 2.84; 95%CI 1.14-7.03, P = 0.02) and the presence of anti-Sm antibodies (OR = 3.11; 95%CI 1.08-8.94; P = 0.03) were significantly more prevalent among lupus patients possessing the TNF-308 A allele. The occurrence of nephritis was also higher in LTA 252 G allele carriers (OR = 2.90; 95%CI 1.12-7.54; P = 0.02). Our results do not support a major role of either the TNF-308 G>A or the LTA 252 A>G polymorphisms as genetic risk factors for SLE. Nevertheless, these polymorphisms appear to associate with the risk of renal lupus and distinct immunological features.
Genetic Polymorphisms of the TNF--and TNF--Genes in Malaysian SLE Patients
A total of 100 SLE patients and 100 normal healthy controls were included in this study. Blood samples were collected and genomic DNA was extracted by using the conventional phenol-chloroform method. The DNA samples were then used to examine the association between the genetic polymorphisms of TNFs and SLE in the Malaysian population. In this study, the distribution pattern of the TNF-308 and TNF-+252 genetic polymorphisms were demonstrated, in addition to their association with susceptibility to SLE. With regards to the TNF-gene polymorphisms, the frequency of the TNF1/1 homozygote was significantly higher (2 = 9.1912, p < 0.05) in healthy controls, while the frequency of TNF1/2 heterozygote was significantly higher ((2 = 9.1912, p < 0.05) in SLE patients. Interestingly, the TNF2/2 homozygote was not present in either SLE patients or in the healthy control group. In terms of the TNF-gene polymorphisms, there was no significant association between the different alleles or genotypes and SLE susceptibility.
Gene, Cell and Tissue
Background: Systemic lupus erythematosus (SLE) is caused by a combination of environmental and genetic factors; studying the association between regulatory genes and this disease may determine the genetic causes of interfering with SLE. In different populations, studies have shown that the tumor necrosis factor α (TNF-α) gene (as a candidate gene) can contribute to the formation and progression of lupus disease. Objectives: This study aimed to indicate the possible association between the increased rate of SLE hazard and 2 single-nucleotide polymorphisms (SNPs) of rs1800629 and rs1800630 genetic polymorphisms in the TNF-α promoter gene in the Lor population. Methods: According to the American College of Rheumatology (ACR) criteria, 120 unrelated SLE patients and 120 healthy controls with no family or personal history of autoimmune diseases were selected. DNA was genotyped for the TNF-α promoter (-308 G/A and -863 C/A) by the tetra-primer amplification-refractory mutation system (tet...