Genetic markers of cardiovascular disease in rheumatoid arthritis
Luis Rodríguez-Rodríguez1, Raquel López-Mejías, Mercedes García-Bermúdez
1Department of Rheumatology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040 Madrid, Spain.
Insights
Genetic factors contribute to cardiovascular disease in rheumatoid arthritis (RA). Specific gene variations, beyond inflammation and traditional risks, are linked to accelerated atherosclerosis in RA patients, necessitating further research.
Area of Science:
- Rheumatology
- Cardiology
- Genetics
Background:
- Cardiovascular (CV) disease is a leading cause of premature death in rheumatoid arthritis (RA) patients, stemming from accelerated atherosclerosis.
- Both RA and atherosclerosis are complex polygenic conditions influenced by genetic factors.
- Chronic inflammation and traditional CV risk factors are implicated, but genetic predispositions are increasingly recognized.
Purpose of the Study:
- To explore the role of genetic factors in the development of atherosclerosis and CV disease in RA patients.
- To identify specific genetic polymorphisms associated with increased CV risk in RA.
Main Methods:
- Review of studies investigating genetic associations with CV disease in RA.
- Analysis of polymorphisms in HLA region (e.g., HLA-DRB1*04) and other inflammatory/metabolic genes (e.g., TNFA, MTHFR, CCR5).
Main Results:
- The HLA-DRB1*04 shared epitope alleles are strongly associated with endothelial dysfunction and CV disease in RA.
- Polymorphisms in TNFA (rs1800629), MTHFR (rs1801131), and CCR5 gene deletions are also linked to CV disease risk in RA patients.
- These genetic factors contribute to atherogenesis in RA beyond chronic inflammation and traditional risk factors.
Conclusions:
- Genetic factors play a significant role in the accelerated atherosclerosis and increased CV disease risk observed in RA.
- Further research is needed to fully elucidate the genetic underpinnings of CV events in RA patients.
Abstract:
Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA.
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