Abstract
Multiple genetic factors contribute to susceptibility to rheumatoid arthritis (RA). The extent of variability in disease presentation in RA may be related to genetic heterogeneity. In this study we investigated the association of the TNF gene polymorphism at position +489 with susceptibility to and severity of RA. Analysis of the frequency of the +489 A and G alleles in a group of 293 consecutive RA patients and 138 healthy controls revealed a significant decrease of the A allele. The +489 GA patients had a 3.9 times decreased chance of having erosive disease than +489 GG patients. These results were confirmed in a prospective study using a cohort of 112 patients who were followed for 12 years. The progression rate of the erosion score over 12 years expressed as Sharp score for X-rays of hands and feet was 3.4 per year for the GA-genotyped patients and 12.1 for the GG-genotyped patients. These associations were independent of rheumatoid factor and HLA-shared epitope positivity. In conclusion, these data suggest that the intron TNF +489 polymorphism is associated with susceptibility to and disease severity of RA independently of HLA-shared epitope-positive alleles.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was financially supported by a grant from the Netherlands Organisation for Scientific Research (NWO) No. 950-10-646.
Rights and permissions
About this article
Cite this article
van Krugten, M., Huizinga, T., Kaijzel, E. et al. Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis. Genes Immun 1, 91–96 (1999). https://doi.org/10.1038/sj.gene.6363632
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363632
Keywords
This article is cited by
-
Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression
BMC Infectious Diseases (2020)
-
Genetic and expression changes in \(\hbox {TNF-}\upalpha \) TNF- α as a risk factor for rheumatoid arthritis pathogenesis in northeast India
Journal of Genetics (2019)
-
TNF-α Gene Polymorphisms: Association with Disease Susceptibility and Response to Anti-TNF-α Treatment in Psoriatic Arthritis
Journal of Investigative Dermatology (2014)
-
Association between TNF-α promoter –308 A/G polymorphism and rheumatoid arthritis: a meta-analysis
Rheumatology International (2014)
-
Association of susceptible genetic markers and autoantibodies in rheumatoid arthritis
Journal of Genetics (2014)