Vascular endothelial growth factor A and cardiovascular disease in rheumatoid arthritis patients
L Rodríguez-Rodríguez1, M García-Bermúdez, C González-Juanatey
1Instituto de Parasitología y Biomedicina Lopez-Neyra, CSIC, Armilla, Granada, Spain.
Insights
Vascular endothelial growth factor A (VEGFA) gene variations do not appear to increase cardiovascular disease risk in rheumatoid arthritis (RA) patients. This study found no significant association between specific VEGFA polymorphisms and cardiovascular events or subclinical atherosclerosis in RA individuals.
Area of Science:
- Genetics and Molecular Biology
- Rheumatology
- Cardiology
Background:
- Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular (CV) disease.
- Vascular Endothelial Growth Factor A (VEGFA) plays a role in angiogenesis and vascular homeostasis.
- Specific polymorphisms in the VEGFA gene may influence CV disease susceptibility.
Purpose of the Study:
- To investigate the association between VEGFA gene polymorphisms (rs2010963 and rs1570360) and the risk of CV disease in patients with RA.
- To evaluate the contribution of these VEGFA polymorphisms to the development of subclinical atherosclerosis in RA patients.
Main Methods:
- Genotyping of VEGFA rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms in 661 RA patients.
- Review of clinical histories for CV events (ischemic heart disease, heart failure, cerebrovascular accident, peripheral arteriopathy).
- Assessment of subclinical atherosclerosis using brachial artery reactivity and carotid artery intima-media thickness in subgroups.
Main Results:
- No significant association was found between VEGFA rs2010963 or rs1570360 polymorphisms and clinically evident CV disease in RA patients.
- These VEGFA polymorphisms were also not significantly associated with the presence of subclinical atherosclerosis (endothelial dysfunction or increased carotid intima-media thickness).
- Neither isolated polymorphisms nor allelic combinations of VEGFA showed a link to increased CV risk in this RA cohort.
Conclusions:
- VEGFA gene polymorphisms rs2010963 and rs1570360 do not appear to be significant risk factors for cardiovascular disease in patients with rheumatoid arthritis.
- These findings suggest that VEGFA genetic variations may not play a substantial role in the pathogenesis of CV complications in RA.
Abstract:
To determine the contribution of the vascular endothelial growth factor A (VEGFA) rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms to the risk of cardiovascular (CV) disease in a series of patients with rheumatoid arthritis (RA). Six hundred sixty-one patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of the Hospital Xeral-Calde, Lugo, and the Hospital San Carlos, Madrid, Spain, were studied. Patients were genotyped for the VEGFA rs2010963 (-634 G>C) and rs1570360 (-1154 G>A) polymorphisms using predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA). Also, human leukocyte antigen (HLA) DRB1 genotyping was performed using molecular-based methods. Clinical histories of the patients were reviewed for the presence of CV events that were considered to be present if the patient had ischemic heart disease, heart failure, cerebrovascular accident, or peripheral arteriopathy. Also, a subgroup of patients without the history of CV events was assessed for the presence of subclinical atherosclerosis manifested by the presence of endothelial dysfunction by brachial artery reactivity (n = 126) and increased carotid artery intima-media thickness (n = 105) using high resolution Doppler ultrasonography. No significant association between the VEGFA rs2010963 and the rs1570360 polymorphisms (neither isolated nor joined as allelic combinations) with clinically evident CV disease was found in this series of patients with RA. It was also the case when we examined the contribution of these polymorphisms to the development of subclinical atherosclerosis. VEGFA polymorphisms do not seem to exert a significant influence on the risk of CV disease in patients with RA.
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