An alternatively spliced soluble TNF-alpha receptor is associated with metabolic disorders: a replication study
| Autor: | Begoña Lainez, Patricia Botas-Cervero, José Manuel Fernández-Real, Wifredo Ricart, Elías Delgado |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Immunology Population Type 2 diabetes chemistry.chemical_compound Insulin resistance Internal medicine Glucose Intolerance medicine Immunology and Allergy Humans Protein Isoforms Receptors Tumor Necrosis Factor Type II Longitudinal Studies education Aged Metabolic Syndrome education.field_of_study business.industry Metabolic disorder Type 2 Diabetes Mellitus Cholesterol LDL Middle Aged medicine.disease Alternative Splicing Endocrinology Cross-Sectional Studies chemistry Diabetes Mellitus Type 2 Uric acid Female Glycated hemoglobin Metabolic syndrome business |
| Zdroj: | Clinical immunology (Orlando, Fla.). 121(2) |
| ISSN: | 1521-6616 |
| Popis: | In a previous study, we identified a biologically active form of tumor necrosis factor-alpha receptor 2 (sTNFR2) produced by differential splicing (DS-TNFR2) which antagonized TNF-α biological activity. Obesity, insulin resistance and type 2 diabetes are linked to increased TNF-α action. We hypothesized that subjects with detectable DS-TNFR2 would be protected from developing obesity and related metabolic disorders. Thus, we investigated if circulating DS-TNFR2 concentration was associated with components of the so-called metabolic syndrome among 269 consecutive subjects from the general population. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Plasma DS-TNFR2 concentration was significantly decreased among patients with glucose intolerance or type 2 diabetes mellitus (p = 0.026). DS-TNFR2 tended to be associated with fasting and post-load glucose (both r = − 0.11, p = 0.054), and with diastolic blood pressure in men (r = − 0.16, p = 0.07). Serum DS-TNFR2 concentration was significantly associated with LDL cholesterol (r = − 0.28, p = 0.002), uric acid (r = − 0.13, p = 0.04) and with blood glycated hemoglobin (r = − 0.13, p = 0.04). DS-TNFR2 declined with increased number of components of the metabolic syndrome (p = 0.03). Those subjects with 2 or more components had significantly decreased circulating DS-TNFR2 levels (0.96 ± 2.2 versus 1.7 ± 3.2, p = 0.033). In summary, the circulating concentration of DS-TNFR2 seems to be inversely linked to metabolic disorders, hinting at a possible anti-inflammatory role. |
| Databáze: | OpenAIRE |
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