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Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA., (© 2011 John Wiley & Sons A/S.)

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., (© 2011 John Wiley & Sons A/S.)

To assess the potential association between ADIPOQ rs266729 and rs1501299 gene polymorphisms, either isolated or in combination, and cardiovascular disease in patients with rheumatoid arthritis (RA), 674 patients seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, were analyzed. Genotyping was performed using predesigned TaqMan assays (Applied Biosystems, Foster City, CA). Carotid intima-media thickness, flow-mediated endothelium-dependent and endothelium-independent post-nitroglycerin vasodilatation, which are used as surrogate markers of subclinical atherosclerosis, were measured in a subsample. No significant differences in the genotype, allele or allele combination frequencies of both polymorphisms were found between RA patients with or without cardiovascular events or subclinical atherosclerosis. Therefore, ADIPOQ rs266729 and rs1501299 polymorphisms do not seem to be associated with cardiovascular disease in RA., (© 2010 John Wiley & Sons A/S.)