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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.)

Objective: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients., Methods: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders., Results: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88)., Conclusion: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.

Objectives: MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA., Methods: 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively., Results: No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05])., Conclusions: Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.

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.)

Objectives: To determine whether the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction or increased carotid intima-media thickness (IMT) in a series of Spanish patients with rheumatoid arthritis (RA)., Methods: Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, were studied. Patients were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. Moreover, between March and December 2007, a subgroup of unselected RA patients with no history of CV events was studied for the presence of subclinical atherosclerosis by the assessment of the endothelial function (n=126) and the carotid artery IMT (n=110) by ultrasonography studies., Results: No significant differences in the allele or genotype frequencies for the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms between RA patients with or without CV events were found. It was also the case when we analysed the potential influence of the genotypes in the presence of endothelial dysfunction or increased carotid artery IMT of patients with RA., Conclusions: Our results do not show that the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may confer a direct risk of CV disease in patients with RA.

Objective: To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the susceptibility to Henoch-Schönlein purpura (HSP) and determine if this polymorphism is implicated in the severity of this systemic vasculitis., Patients and Methods: Fifty-seven unselected patients from Northwest Spain with primary systemic vasculitis, classified as HSP according to previously proposed criteria, with a follow-up of at least 2 years and 229 healthy controls, were included in this study. All the individuals were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real time PCR technology, using TaqMan 5' allelic discrimination assay., Results: No significant differences in allele or genotype distribution frequencies for the PTPN22 gene polymorphism were observed between HSP patients and controls. It was also the case when HSP patients were stratified for the presence of severe gastrointestinal complications (n = 46), nephritis (n= 37) or permanent renal involvement (renal sequelae) (n = 12)., Conclusion: Our results do not support a potential implication of the PTPN22 gene polymorphism in the susceptibility to and clinical expression of HSP.

Objective: To assess whether polymorphism of the interleukin (IL)-6 gene at the position -174 was implicated in the incidence of Henoch-Schönlein pur-pura (HSP). A further objective was to determine if any relationship existed with severe systemic complications of HSP, in particular with severe renal and gastrointestinal involvement., Methods: Unselected patients from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients included in the present study were required to have had at least 2 year's follow-up. Patients and controls were genotyped for a single biallelic (G/C) nucleotide polymorphism in the promoter region at the position -174 of the IL-6 gene by a polymerase reaction chain-restriction fragment length polymorphism (PCR-RFLP) method., Results: Forty-six Caucasian HSP patients and 124 healthy matched controls were studied. No allele or genotype differences between the whole group of HSP and controls were observed. This was also the case when HSP patients were stratified by the presence of gastrointestinal complications, nephritis, and permanent renal involvement (renal sequelae)., Conclusion: The polymorphism in IL-6 gene promoter (-174 G/C) does not appear to be a genetic risk factor for HSP in Northwest Spain.

Objective: To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at position -173 was implicated in the incidence of Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA). A further objective was to determine if any relationship existed with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction., Methods: Unselected patients from Northwest Spain with primary cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV) according to proposed criteria were studied. Patients with HV were included in this study if they fulfilled the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. Patients and controls were genotyped for a single nucleotide polymorphism (SNP) in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100)., Results: Ninety-five Caucasian patients (57 classified as having HSP and 38 who fulfilled definitions for CLA) and 122 healthy controls were studied. No allele or genotype differences between the whole group of HSP or CLA patients and controls were observed. This was also the case when HSP patients were stratified by the presence of gastrointestinal complications, nephritis, and permanent renal involvement (renal sequelae)., Conclusion: The polymorphism in MIF gene promoter (-173 G/C) does not appear to be genetic risk factors for cutaneous vasculitis in Northwest Spain.