scholarly journals Single-nucleotide polymorphisms in tumor necrosis factor receptor genes: Definition of novel haplotypes and racial/ethnic differences

2002 ◽  
Vol 46 (8) ◽  
pp. 2045-2050 ◽  
Author(s):  
S. Louis Bridges ◽  
Grace Jenq ◽  
Molly Moran ◽  
Tamara Kuffner ◽  
William C. Whitworth ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Single Nucleotide Polymorphisms ◽  
Ethnic Differences ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Definition Of ◽  
Racial Ethnic ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor (TNF)-α gene +489 polymorphisms: association with psoriatic arthritis

2013 ◽  
Vol 86 (1) ◽  
Author(s):  
G. Murdaca ◽  
F. Puppo
Keyword(s):  
Psoriatic Arthritis ◽  
Tumor Necrosis Factor ◽  
Single Nucleotide Polymorphisms ◽  
Tumor Necrosis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Tnf Α ◽  
The Difference ◽  
Necrosis Factor

Objective of this work was to investigate the role of single nucleotide polymorphisms (SNPs) at position +489 of the tumor necrosis factor (TNF)-α gene in generic susceptibility and severity of psoriatic arthritis (PsA). Fifty-seven Caucasian PsA patients diagnosed according to CASPAR criteria and 155 healthy matched controls were studied. PASI score, DAS28 and Disability INdex HAQ were calculated. Genomic DNA was extracted from peripheral blood samples and SNPs +489 G>A (rs 80267959) were amplified by PCR. The SNP +489 genotype was significantly associated with PsA susceptibility (p=0.0136) and severity of clinical and laboratory parameters (p values ranging from 0.016 to 2.908 x 10-12). The difference in severity was accounted for by the difference between the AA and GA genotypes with respect to the GG genotype. These findings suggest that TNF-α gene polymorphisms may influence PsA susceptibility and severity. Psoriatics arthritis (PsA) is a complex immunemediated disease that results from the interplay between multiple genetic and environmental factor [1]. Although the pathogenesis of PsA remains elusive, there is evidence that genetic factors may contribute to the etiology of the disease [2]. Is has been estimated that at least one third of the genetic contribution to PsA resides in the major histocompatibility complex (MHC) region [2]. The tumor necrosis factor (TNF)-α gene, which is located in the short arm of chromosome 6 in the MHC class III region between the HLA-B and HLA-DR genes, has been proposed as a major candidate gene in PsA [3]. This hypothesis is supported by studies which have found high serum, synovial fluid and synovial membrane TNF-α levels in patients with PsA [4,5]. Several single nucleotide polymorphisms (PNPs) have been identified in the TNF-α gene promoter [6]. In particular, two common polymorphisms, namely G to A substitutions at positions -238 and -308 have been studied in patients with PsA. However, association studies of these two TNF-α polymorphisms and genetic susceptibility to PsA have lead to conflicting results [7-12]. Previous studies have indicated the potential role of the SNP at +489 position in the first intron of the TNF-α gene in the susceptibility to some rheumatic autoimmune diseases like rheumatoid arthritis [13], systemic lupus erythematosus [14] and systemic sclerosis [15]. However, to our present knowledge, studies on the association of +489 polymorphism with PsA susceptibility and response to TNF-α inhibitors are not reported in the literature. Is this study we investigated the role of SNPs at +489 within the TNF-α gene in PsA susceptibility and severity.

Abstract 291: Association of Single Nucleotide Polymorphisms in Inflammatory Candidate Genes with Circulating Inflammatory Biomarker Concentrations: The Framingham Heart Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Renate Schnabel ◽  
Kathryn L Lunetta ◽  
Martin G Larson ◽  
Josée Dupuis ◽  
John F Keaney ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Single Nucleotide Polymorphisms ◽  
Tumor Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Candidate Gene Approach ◽  
Nucleotide Polymorphisms ◽  
Q Value ◽  
Single Nucleotide ◽  
Inflammatory Biomarker ◽  
Necrosis Factor

Background : Chronic subclinical inflammation is a prominent feature of atherosclerotic disease. The genetic background for this pro-inflammatory state is not well-established. Circulating biomarker concentrations have become attractive candidates to measure disease activity and prognosis. Methods : We examined 2356 single-nucleotide polymorphisms (SNPs) in 235 inflammatory pathway genes in association with 11 circulating inflammatory biomarkers in about 1800 Framingham Offspring cohort participants [CD40 ligand, CRP, intercellular adhesion molecule-1, interleukin-6 (IL6), urinary isoprostanes, monocyte chemoattractant protein-1 (MCP1), myeloperoxidase, P-selectin, tumor necrosis factor alpha, tumor necrosis factor receptor-2, fibrinogen]. We created residuals of log transformed biomarker concentrations adjusting for 16 potential confounders. Only SNPs with call rate ≥0.98 and HWE p>0.01, which had at least 5 minor allele carriers entered analyses. False discovery rate (FDR) and q-value methods were applied. Results : We observed similar results with FDR and q-value methods. A total of 45 associations were significant at a cutoff q value of 0.25. The top SNPs were observed in the SELP gene in association with P-selectin concentrations (rs6136 [nonsynonymous], p= 5.17*10 −39 , rs3753305 [intronic], p= 6.17*10 −9 ) and the ICAM1 gene in relation to ICAM-1 concentrations (rs1799969 [coding-nonsynonymous], p= 1.32*10 −8 ). Lowest p-values for trans-acting SNPs were observed for APCS (rs1374486 [function unknown], p= 1.01*10 −7 , and rs6695377 [function unknown], p= 1.85*10 −7 ) with MCP-1 concentrations and for IL6R (rs8192284 [coding-nonsynonimous,intronic], p= 3.36*10 −5 ) with IL6 concentrations. In addition, we could replicate reported findings for rs1799969, and rs5498 in the ICAM-1 gene in relation to ICAM-1 concentrations as well as associations of SNPs rs2857654, rs1024611, and rs2857657 in the CCL-2 gene with MCP-1 concentrations. Conclusions : The results of this candidate gene approach support the relevance of genetic variation for circulating inflammatory biomarker traits. Some former findings were confirmed and novel potential candidates are reported. Our findings merit replication in other cohorts.

scholarly journals Single Nucleotide Polymorphisms of the Inflamatory Cytokine Genes: Interleukin-1B, Tumor Necrosis Factors-A and Tumor Necrosis Factor-B in Adult Patients with Immune / Thrombocytopenia Единечни Нуклеотидни Полиморфизми Во Цитокинските Гени: Интерлеукин-1Б, Тумор Некрозис Фактор-А И Тумор Некрозис Фактор-Б Кај Пациенти Со Имуна Тромбоцитопенија

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 109-115 ◽  
Author(s):  
Marica Pavkovic ◽  
Rosica Angelovic ◽  
Marija Popova-Simjanovska ◽  
Oliver Karanfilski ◽  
Slobodanka Trpkovska-Terzieva ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Single Nucleotide Polymorphisms ◽  
Immune Thrombocytopenia ◽  
Tumor Necrosis ◽  
Allele Frequencies ◽  
Adult Patients ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Necrosis Factor

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia due to platelet autoantibodies, causing an accelerated clearance of opsonized platelets by phagocytes. The etiology of ITP remains unclear, both genetic and environmental factors may have a role in the disease development. The aim of our study was to investigate a possible association of three single nucleotide polymorphisms (SNP) in the genes for interleukin beta (IL1B-511C/T), tumor necrosis factor beta (TNF+252G/A) and tumor necrosis factor alpha (TNFA-308G/A) with ITP. We have analyzed 125 adult patients with ITP and 120 healthy matched controls. Genotyping was performed by using PCR- RFLP methods. Our results demonstrated significantly different genotype distributions and allele frequencies for TNFB+252G/A in patients with ITP, p = 0.005 and p = 0.009 with Yates correction. We did not find any significant differences in the genotype distribution or allele frequencies for the other two genes. We have found significantly different genotype distribution and allele frequencies for TNFA- 308G/A between patients with unresponsive and responsive ITP patients, p = 0.016 and p = 0.009. There were no significant differences in genotype distribution and allele frequencies for ILB-511C/T and TNFB+252G/A polymorphisms between those two groups of patients. We did not find any significant differences in genotype distribution and allele frequencies for all three polymorphisms between splenectomized and unsplenectomized ITP patients. The obtained data indicate that the A allele of TNFB+252G/A is more frequent in these patients than in the controls and that this polymorphism may play a significant role in disease susceptibility. The A allele of TNFA-308G/A was more frequent in patients with unresponsive ITP, indicating that this gene polymorphisms may contribute to therapy resistance.

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