Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients
Single nucleotide polymorphism (SNP) in the human Tumor Necrosis Factor-α(TNF-α) gene promoter, the −308 G/A variant, has been associated with increased TNF-α levels that may amplify the severity of rheumatoid arthritis (RA) and a poor responsiveness to TNF-α blockade therapy. High mobility group bo...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2012-09-01
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| Series: | European Journal of Inflammation |
| Online Access: | https://doi.org/10.1177/1721727X1201000316 |
| _version_ | 1818402210777661440 |
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| author | A. Bitto F. Polito G. Bagnato R. Talotta M. Atteritano N. Irrera R. Ientile N. Ferlazzo D. Caccamo G. Bagnato A. Caliri F. Squadrito D. Altavilla |
| author_facet | A. Bitto F. Polito G. Bagnato R. Talotta M. Atteritano N. Irrera R. Ientile N. Ferlazzo D. Caccamo G. Bagnato A. Caliri F. Squadrito D. Altavilla |
| author_sort | A. Bitto |
| collection | DOAJ |
| description | Single nucleotide polymorphism (SNP) in the human Tumor Necrosis Factor-α(TNF-α) gene promoter, the −308 G/A variant, has been associated with increased TNF-α levels that may amplify the severity of rheumatoid arthritis (RA) and a poor responsiveness to TNF-α blockade therapy. High mobility group box protein (HMGB-1) is a pro-inflammatory cytokine that plays a pivotal role in the pathogenesis of RA and may be an original target of therapy. The aim of this study is to investigate whether the −308 G/A variant of the TNF-α gene is associated with altered expression of HMBG-1. A total of 110 consecutive patients with rheumatoid arthritis and spondylo-arthritis (ankylosing spondylitis, psoriatic arthritis and spondylitis associated with inflammatory bowel disease) referring to the Rheumatology Unit of Messina University Hospital were enrolled. Patients were genotyped for the −308 TNF-α gene promoter polymorphism. Clinical status was also assessed. HMGB-1 and TNF-α mRNA(Real Time PCR) from total blood and plasmatic HMGB-1 (Western Blot analysis) and TNF-α (ELISA) protein were also evaluated. Irrespective of the underlying disease, patients carrying the G/A genotype showed enhanced HMGB-1 and TNF-α mRNA levels and increased circulating concentration of the inflammatory cytokines when compared to patients with G/G genotype. The data suggest that subjects carrying the TNF-α −308G/A genotype have enhanced expression of HMGB-1 protein that may explain, at least in part, the increased severity of the disease. |
| first_indexed | 2024-12-14T08:04:45Z |
| format | Article |
| id | doaj.art-d087c0f6326b405ea895b35e9dfcb53f |
| institution | Directory Open Access Journal |
| issn | 1721-727X |
| language | English |
| last_indexed | 2024-12-14T08:04:45Z |
| publishDate | 2012-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | European Journal of Inflammation |
| spelling | doaj.art-d087c0f6326b405ea895b35e9dfcb53f2022-12-21T23:10:15ZengSAGE PublishingEuropean Journal of Inflammation1721-727X2012-09-011010.1177/1721727X1201000316Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis PatientsA. Bitto0F. Polito1G. Bagnato2R. Talotta3M. Atteritano4N. Irrera5R. Ientile6N. Ferlazzo7D. Caccamo8G. Bagnato9A. Caliri10F. Squadrito11D. Altavilla12 Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy Department of Internal Medicine, Rheumatology Unit, University of Messina, Italy Department of Internal Medicine, Rheumatology Unit, University of Messina, Italy Department of Internal Medicine, Rheumatology Unit, University of Messina, Italy Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Italy Department of Internal Medicine, Rheumatology Unit, University of Messina, Italy Department of Internal Medicine, Rheumatology Unit, University of Messina, Italy Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Italy Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, ItalySingle nucleotide polymorphism (SNP) in the human Tumor Necrosis Factor-α(TNF-α) gene promoter, the −308 G/A variant, has been associated with increased TNF-α levels that may amplify the severity of rheumatoid arthritis (RA) and a poor responsiveness to TNF-α blockade therapy. High mobility group box protein (HMGB-1) is a pro-inflammatory cytokine that plays a pivotal role in the pathogenesis of RA and may be an original target of therapy. The aim of this study is to investigate whether the −308 G/A variant of the TNF-α gene is associated with altered expression of HMBG-1. A total of 110 consecutive patients with rheumatoid arthritis and spondylo-arthritis (ankylosing spondylitis, psoriatic arthritis and spondylitis associated with inflammatory bowel disease) referring to the Rheumatology Unit of Messina University Hospital were enrolled. Patients were genotyped for the −308 TNF-α gene promoter polymorphism. Clinical status was also assessed. HMGB-1 and TNF-α mRNA(Real Time PCR) from total blood and plasmatic HMGB-1 (Western Blot analysis) and TNF-α (ELISA) protein were also evaluated. Irrespective of the underlying disease, patients carrying the G/A genotype showed enhanced HMGB-1 and TNF-α mRNA levels and increased circulating concentration of the inflammatory cytokines when compared to patients with G/G genotype. The data suggest that subjects carrying the TNF-α −308G/A genotype have enhanced expression of HMGB-1 protein that may explain, at least in part, the increased severity of the disease.https://doi.org/10.1177/1721727X1201000316 |
| spellingShingle | A. Bitto F. Polito G. Bagnato R. Talotta M. Atteritano N. Irrera R. Ientile N. Ferlazzo D. Caccamo G. Bagnato A. Caliri F. Squadrito D. Altavilla Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients European Journal of Inflammation |
| title | Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients |
| title_full | Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients |
| title_fullStr | Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients |
| title_full_unstemmed | Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients |
| title_short | Influence of Polymorphism −308 G/A of the Tnf-α Gene on High Mobility Group Box-1 Protein in Rheumatoid and Spondylo-Arthritis Patients |
| title_sort | influence of polymorphism 308 g a of the tnf α gene on high mobility group box 1 protein in rheumatoid and spondylo arthritis patients |
| url | https://doi.org/10.1177/1721727X1201000316 |
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