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 ( , rs1800629) of the TNFA locus, the rs1801131 polymorphism ( ; 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. 1. Introduction Many epidemiological studies have reported in a consistent way an increased risk of nearly all forms of cardiovascular (CV) disease, a higher prevalence of subclinical atherosclerosis, and an increased CV mortality among rheumatoid arthritis (RA) patients [1, 2]. However, traditional CV risk factors, such as hypertension or diabetes mellitus, are not substantially different in RA compared to general population [3, 4]. Therefore, these risk factors may not account for the difference in risk between RA and the general population, and RA-associated factors, such as systemic inflammation, must be the main contributors to the observed gap [5]. Both RA and atherosclerosis are chronic inflammatory diseases [6, 7] that exhibit similar pathophysiological mechanisms [8], and that display a strong genetic component of susceptibility [9–11]. RA has an estimated heritability of up to 60% [12] and CV disease in the general population of up to 30–60% [13]. Besides, a specific genetic background may contribute to the development of both diseases [14]. Subclinical atherosclerosis is present in patients with RA [15, 16]. Noninvasive surrogate markers of atherosclerosis, such as the presence of endothelial dysfunction (established as an impaired flow-mediated endothelium-dependent vasodilatation FMD by brachial ultrasonography) or an abnormally increased
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