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

被引:115
作者
Rodriguez-Rodriguez, Luis [2 ,3 ]
Gonzalez-Juanatey, Carlos [4 ]
Palomino-Morales, Rogelio [2 ]
Vazquez-Rodriguez, Tomas R.
Miranda-Filloyd, Jose A. [5 ]
Fernandez-Gutierrez, Benjamin [3 ]
Llorca, Javier [6 ,7 ]
Martin, Javier [2 ]
Gonzalez-Gay, Miguel A. [1 ]
机构
[1] Hosp Univ Marques Valdecilla, IFIMAV, Dept Rheumatol, Santander 39008, Spain
[2] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain
[3] Hosp Clin San Carlos, Dept Rheumatol, Madrid 28040, Spain
[4] Hosp Xeral Calde, Div Cardiol, Lugo 27004, Spain
[5] Hosp Xeral Calde, Dept Rheumatol, Lugo 27004, Spain
[6] Univ Cantabria, Sch Med, Dept Epidemiol & Computat Biol, Santander 39011, Spain
[7] IFIMAV, CIBERESP, Santander 39011, Spain
关键词
Rheumatoid arthritis; Atherosclerosis; Cardiovascular disease; Genetics; TNFA; rs1800629; TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; CORONARY-ARTERY DISEASE; INTIMA-MEDIA THICKNESS; PROMOTER POLYMORPHISM; MYOCARDIAL-INFARCTION; TNF-ALPHA; ENDOTHELIAL FUNCTION; HEART-DISEASE; ATHEROSCLEROSIS;
D O I
10.1016/j.atherosclerosis.2010.10.052
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:125 / 130
页数:6
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