Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (168)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Skoog, T.
Right arrow Articles by Hamsten, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Skoog, T.
Right arrow Articles by Hamsten, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol 8, 1443-1449, Copyright © 1999 by Oxford University Press

ARTICLES

A common functional polymorphism (C-->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha

T Skoog, FM van't Hooft, B Kallin, S Jovinge, S Boquist, J Nilsson, P Eriksson and A Hamsten
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska Hospital, S-171 76 Stockholm, Sweden. tiinasko@instmed.ks.se

Tumour necrosis factor-alpha (TNF-alpha) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF-alpha has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance.The regulation of TNF-alpha expression in man is indicated to be partly genetically determined. We therefore screened a 1263 bp section of the proximal promoter of the TNF-alpha gene for common genetic variants affecting the transcriptional activity of the gene. Here we report the characterization of a common functional polymorphism in the promoter region of the TNF-alpha gene, a C-->A substitution at position -863. Electromobility shift assays provided evidence for a distinct difference in the binding of monocytic and hepatic nuclear factors to the -863C and -863A alleles. The rare -863A allele was associated with 31% lower transcriptional activity ( P < 0.001) in chloramphenicol acetyltransferase (CAT) reporter gene studies in human hepatoblastoma (HepG2) cells, indicating that the-863C/A polymorphism influences the basal rate of transcription of the TNF- alpha gene in vitro. Allele frequencies were 0.83/0.17 amongst 254 apparently healthy men of Swedish origin, aged 35-50 years. In 156 men, the -863C/A polymorphism was associated with the serum TNF-alpha concentration, carriers of the rare A allele having a significantly lower TNF-alpha level ( P < 0.05). It is concluded that the common- 863C/A polymorphism in the promoter region of the TNF-alpha gene is functional in vitro in monocytic and hepatic cells and influences the serum TNF-alpha concentration in vivo in healthy middle-aged men.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
A. L. Van Dyke, M. L. Cote, A. S. Wenzlaff, W. Chen, J. Abrams, S. Land, C. N. Giroux, and A. G. Schwartz
Cytokine and Cytokine Receptor Single-Nucleotide Polymorphisms Predict Risk for Non-Small Cell Lung Cancer among Women
Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1829 - 1840.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. Liu, E. J. Metter, L. Ferrucci, and S. M. Roth
TNF promoter polymorphisms associated with muscle phenotypes in humans
J Appl Physiol, September 1, 2008; 105(3): 859 - 867.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
Y.-f. Cheung, G.-y. Huang, S.-b. Chen, X.-q. Liu, L. Xi, X.-c. Liang, M.-r. Huang, S. Chen, L.-s. Huang, X.-q. Liu, et al.
Inflammatory Gene Polymorphisms and Susceptibility to Kawasaki Disease and Its Arterial Sequelae
Pediatrics, September 1, 2008; 122(3): e608 - e614.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. W. Hsing, L. C. Sakoda, A. Rashid, G. Andreotti, J. Chen, B.-S. Wang, M.-C. Shen, B. E. Chen, P. S. Rosenberg, M. Zhang, et al.
Variants in Inflammation Genes and the Risk of Biliary Tract Cancers and Stones: A Population-Based Study in China
Cancer Res., August 1, 2008; 68(15): 6442 - 6452.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. R. Gingo, L. J. Silveira, Y. E. Miller, A. L. Friedlander, G. P. Cosgrove, E. D. Chan, L. A. Maier, and R. P. Bowler
Tumour necrosis factor gene polymorphisms are associated with COPD
Eur. Respir. J., May 1, 2008; 31(5): 1005 - 1012.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
S.-J. Chang, P.-C. Tsai, C.-J. Chen, H.-M. Lai, and Y.-C. Ko
The polymorphism -863C/A in tumour necrosis factor-{alpha} gene contributes an independent association to gout
Rheumatology, November 1, 2007; 46(11): 1662 - 1666.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
K. Oda, N. Tanaka, T. Arai, J. Araki, Y. Song, L. Zhang, A. Kuchiba, T. Hosoi, T. Shirasawa, M. Muramatsu, et al.
Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases
Hum. Mol. Genet., March 15, 2007; 16(6): 592 - 599.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. P. Purdue, Q. Lan, A. Kricker, A. E. Grulich, C. M. Vajdic, J. Turner, D. Whitby, S. Chanock, N. Rothman, and B. K. Armstrong
Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study
Carcinogenesis, March 1, 2007; 28(3): 704 - 712.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. Sharma, A. Sharma, S. Kumar, S. K. Sharma, and B. Ghosh
Association of TNF Haplotypes with Asthma, Serum IgE Levels, and Correlation with Serum TNF-{alpha} Levels
Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 488 - 495.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
E. M. Ramos, M.-T. Lin, E. B. Larson, I. Maezawa, L.-H. Tseng, K. L. Edwards, G. D. Schellenberg, J. A. Hansen, W. A. Kukull, and L.-W. Jin
Tumor Necrosis Factor {alpha} and Interleukin 10 Promoter Region Polymorphisms and Risk of Late-Onset Alzheimer Disease.
Arch Neurol, August 1, 2006; 63(8): 1165 - 1169.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Ma, G. Ruan, Y. Wang, Q. Li, P. Zhu, Y.-Z. Qin, J.-L. Li, Y.-R. Liu, D. Ma, and H. Zhao
Two Single-Nucleotide Polymorphisms with Linkage Disequilibrium in the Human Programmed Cell Death 5 Gene 5' Regulatory Region Affect Promoter Activity and the Susceptibility of Chronic Myelogenous Leukemia in Chinese Population
Clin. Cancer Res., December 15, 2005; 11(24): 8592 - 8599.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
P. S. Monraats, N. M. M. Pires, A. Schepers, W. R. P. Agema, L. S. M. Boesten, M. R. de Vries, A. H. Zwinderman, M. P. M. de Maat, P. A. F. M. Doevendans, R. J. de Winter, et al.
Tumor necrosis factor-{alpha} plays an important role in restenosis development
FASEB J, December 1, 2005; 19(14): 1998 - 2004.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
F Navaglia, D Basso, C-F Zambon, E Ponzano, L Caenazzo, N Gallo, A Falda, C Belluco, P Fogar, E Greco, et al.
Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals
J. Med. Genet., June 1, 2005; 42(6): 503 - 510.
[Full Text] [PDF]

Home page
 JBJSHome page
T. O. White, P. J. Jenkins, R. D. Smith, C. W.J. Cartlidge, and C. M. Robinson
The Epidemiology of Posttraumatic Adult Respiratory Distress Syndrome
J. Bone Joint Surg. Am., November 1, 2004; 86(11): 2366 - 2376.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
T. Asghar, S. Yoshida, S. Kennedy, K. Negoro, W. Zhuo, S. Hamana, S. Motoyama, S. Nakago, D. Barlow, and T. Maruo
The tumor necrosis factor-{alpha} promoter -1031C polymorphism is associated with decreased risk of endometriosis in a Japanese population
Hum. Reprod., November 1, 2004; 19(11): 2509 - 2514.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
S. L. Ma, N. L.S. Tang, L. C.W. Lam, and H. F.K. Chiu
Association between tumor necrosis factor-{alpha} promoter polymorphism and Alzheimer's disease
Neurology, January 27, 2004; 62(2): 307 - 309.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
M. Heesen, D. Kunz, M. Wessiepe, T. van der Poll, A. H. Zwinderman, and B. Blomeke
Rapid Genotyping for Tumor Necrosis Factor-{alpha} (TNF-{alpha}) -863C/A Promoter Polymorphism That Determines TNF-{alpha} Response
Clin. Chem., January 1, 2004; 50(1): 226 - 228.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y. J. Kim, H.-S. Lee, J.-H. Yoon, C. Y. Kim, M. H. Park, L. H. Kim, B. L. Park, and H. D. Shin
Association of TNF-{alpha} promoter polymorphisms with the clearance of hepatitis B virus infection
Hum. Mol. Genet., October 1, 2003; 12(19): 2541 - 2546.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
L. Giordani, P. Bruzzi, C. Lasalandra, M. Quaranta, F. Schittulli, F. Della Ragione, and A. Iolascon
Association of Breast Cancer and Polymorphisms of Interleukin-10 and Tumor Necrosis Factor-{alpha} Genes
Clin. Chem., October 1, 2003; 49(10): 1664 - 1667.
[Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
S. Tuglular, P. Berthoux, and F. Berthoux
Polymorphisms of the tumour necrosis factor {alpha} gene at position -308 and TNFd microsatellite in primary IgA nephropathy
Nephrol. Dial. Transplant., April 1, 2003; 18(4): 724 - 731.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Amicosante, F. Berretta, A. Franchi, P. Rogliani, C. Dotti, M. Losi, R. Dweik, and C. Saltini
HLA-DP-unrestricted TNF-{alpha} release in beryllium-stimulated peripheral blood mononuclear cells
Eur. Respir. J., November 1, 2002; 20(5): 1174 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Shen, L. Wang, M. R. Spitz, W. K. Hong, L. Mao, and Q. Wei
A Novel Polymorphism in Human Cytosine DNA-Methyltransferase-3B Promoter Is Associated with an Increased Risk of Lung Cancer
Cancer Res., September 1, 2002; 62(17): 4992 - 4995.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. A. van Heel, I. A. Udalova, A. P. De Silva, D. P. McGovern, Y. Kinouchi, J. Hull, N. J. Lench, L. R. Cardon, A. H. Carey, D. P. Jewell, et al.
Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-{kappa}B transcription factors
Hum. Mol. Genet., May 16, 2002; 11(11): 1281 - 1289.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
T. Skoog, W. Dichtl, S. Boquist, C. Skoglund-Andersson, F. Karpe, R. Tang, M.G. Bond, U. de Faire, J. Nilsson, P. Eriksson, et al.
Plasma tumour necrosis factor-{alpha} and early carotid atherosclerosis in healthy middle-aged men
Eur. Heart J., March 1, 2002; 23(5): 376 - 383.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
B. A. Hendrickson, R. Gokhale, and J. H. Cho
Clinical Aspects and Pathophysiology of Inflammatory Bowel Disease
Clin. Microbiol. Rev., January 1, 2002; 15(1): 79 - 94.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. J. Post, R. Laham, F. W. Sellke, and M. Simons
Therapeutic angiogenesis in cardiology using protein formulations
Cardiovasc Res, February 16, 2001; 49(3): 522 - 531.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
I. A. Udalova, A. Richardson, A. Denys, C. Smith, H. Ackerman, B. Foxwell, and D. Kwiatkowski
Functional Consequences of a Polymorphism Affecting NF-kappa B p50-p50 Binding to the TNF Promoter Region
Mol. Cell. Biol., December 15, 2000; 20(24): 9113 - 9119.
[Abstract] [Full Text]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.