TNFA -308 (rs1800629) polymorphism is associated with a higher risk of cardiovascular disease in patients with rheumatoid arthritis

Atherosclerosis. 2011 May;216(1):125-30. doi: 10.1016/j.atherosclerosis.2010.10.052. Epub 2011 Feb 24.


Objective: To assess the influence of the TNFA rs1800629 (G > A) polymorphism in the risk of cardiovascular (CV) disease and subclinical atherosclerosis in patients with rheumatoid arthritis (RA).

Methods: 587 patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were studied. Patients were genotyped for the TNFA rs1800629 polymorphism using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Carotid artery intima-media thickness, flow-mediated endothelium-dependent and endothelium independent vasodilatation, used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients.

Results: We observed a higher frequency of carriers of the minor allele A among the patients with CV disease (with 37.6% vs. without 27.9%, p = 0.06, OR 1.56 [95% confidence interval-CI 0.95-2.54]). Carriers of the minor allele A exhibited a higher risk of CV events after adjustment for demographic and traditional CV risk factors (p = 0.023, HR 1.72 [95% CI 1.076-2.74]). Also, a significant interaction between this polymorphism and the presence of the rheumatoid shared epitope (SE) was observed (p = 0.024). Due to this, the association between carriers of the minor allele A and CV disease was only present in carriers of the SE, even after adjustment (p = 0.001, HR 2.43 [95% CI 1.41-4.19]). No significant association between the TNFA variant and the surrogate markers of subclinical atherosclerosis was observed.

Conclusion: Our results show that TNFA rs1800629 gene polymorphism is associated with predisposition to CV complications in patients with RA. This predisposition is restricted to individuals carrying the rheumatoid SE.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Brachial Artery / physiopathology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Carotid Arteries / pathology
  • Carotid Artery Diseases / genetics*
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / pathology
  • Chi-Square Distribution
  • Epitopes
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-DR Antigens / genetics
  • HLA-DR3 Antigen / genetics
  • HLA-DRB1 Chains
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Spain
  • Tumor Necrosis Factor-alpha / genetics*
  • Vasodilation


  • Epitopes
  • HLA-DR Antigens
  • HLA-DR3 Antigen
  • HLA-DRB1 Chains
  • Tumor Necrosis Factor-alpha