Letters to the editor4.

Analysis of the influence of the ghrelin receptor rs509035, rs512692 and rs2922126 polymorphisms in the risk of cardiovascular disease in patients with rheumatoid arthritis Sirs, Cardiovascular (CV) events due to accelerated atherosclerosis constitute the leading cause of mortality in patients with rheuma-toid arthritis (RA) (1). Chronic systemic inflammation predicts the progression of atherosclerosis and contributes to the increased incidence of CV events observed in RA (2). The mechanisms involved in inflammation related CV disease in RA require further study. Ghrelin is a 28-amino-acid gastric peptide that was discovered in 1999 and was identified as the endogenous ligand for the growth hormone secretagogue receptor (3). Ghrelin receptor (GHSR) is a seven-transmembrane domain G protein-coupled receptor located both in the central nervous system (the pituitary and hypothalamus) and in a wide variety of peripheral tissues including the heart, blood vessels and endothelial cells (4). The ghrelin/GHSR system exerts antiinflam-matory effects, both inhibiting proinflam-matory cytokine release (IL-1beta, IL-6, and TNF-alpha) in monocytes, T cells and endothelial cells and increasing the production of antiinflammatory cytokines and chemokines (5). This system also appears to exert a cardioprotective effect, protecting myocites against ischaemia and having cardiotropic actions (6). In RA the ghrelin/GHSR system also seems to exert a protective effect in the vascular system. We reported that anti-TNF-α therapy increased serum levels of ghrelin (7), which, in turn, was associated with a reductions in soluble P-selectin serum level, a biomarker of endothelial activation that predicts CV event rates. Polymorphisms located in the GHSR gene have been associated with CV disease and classic CV risk factors (6) In the present study we assessed for first time the potential the effect of tree polymorphisms the GHSR gene (8) on the risk of clinically evident CV disease in patients with RA. Six hundred and fifty-nine consecutive patients , fulfilling the 1987 American College of Rheumatology classification criteria for RA (9), seen at the rheumatology outpatient assessed for the GHSR rs509035, rs512692 and rs2922126 polymorphisms. Patients were genotyped for the GHSR polymor-phisms using predesigned TaqMan single nucleotide polymorphism genotyping assay as previously reported (8). Also, HLA-DRB1 genotyping was performed using molecular based methods. A CV event was considered to be present if the patient had ischaemic heart disease, heart failure, cerebrovascular accident or peripheral arteriopathy. The local institutional committees approved the study. No deviation from Hardy-Weinberg equilibrium for any GHSR polymorphisms was found in patients with or without CV events. …