title: TNFA -308 (rs1800629) polymorphism is associated with a higher risk of cardiovascular disease in patients with rheumatoid arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Granada 18100, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodríguez-Rodríguez
authors.forename: Carlos
authors.initials: C
authors.lastname: González-Juanatey
authors.forename: Rogelio
authors.initials: R
authors.lastname: Palomino-Morales
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Vázquez-Rodríguez
authors.forename: José A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fernández-Gutiérrez
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics* / Q000276:immunology; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016009:Chi-Square Distribution; D000939:Epitopes; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014664:Vasodilation
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha