Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Arthritis Rheumatol ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30251476

RESUMO

OBJECTIVE: A genome-wide association study (GWAS) was conducted to shed light into the genetic background influencing the development of cardiovascular (CV) disease in patients diagnosed with rheumatoid arthritis (RA). METHODS: After quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analysed in 2,989 RA patients from European origin. Data on subclinical atherosclerosis, obtained by carotid ultrasonography through assessment of carotid intima-media thickness (cIMT) and presence/absence of carotid plaques, were available for 1,355 individuals. RESULTS: A genetic variant of the RARB gene (rs116199914) was associated with cIMT values at the genome-wide level of significance (minor allele (G): beta (ß) coefficient=0.142, P=1.86E-08). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biological pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (GO:0032964, PFDR =4.01E-03). Furthermore, our data suggest a potential influence of the previously described candidate CV risk loci NFKB1, MSRA and ZC3HC1 (P=8.12E-04, P=5.94E-04 and P=2.46E-04, respectively). CONCLUSION: Our study strongly suggests that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA. This article is protected by copyright. All rights reserved.

2.
Arthritis Rheumatol ; 70(11): 1829-1834, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29781588

RESUMO

OBJECTIVE: Data on the role of tobacco exposure in systemic sclerosis (SSc; scleroderma) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations, based on the European Scleroderma Trials and Research group database. METHODS: Adult SSc patients with data on smoking history and a 12-24-month follow-up visit were included. Associations of severity and progression of organ involvement with smoking history and the Comprehensive Smoking Index were assessed using multivariable regression analyses. RESULTS: A total of 3,319 patients were included (mean age 57 years, 85% female); 66% were never smokers, 23% were ex-smokers, and 11% were current smokers. Current smokers had a lower percentage of antitopoisomerase autoantibodies than previous or never smokers (31% versus 40% and 45%, respectively). Never smokers had a higher baseline forced expiratory volume in 1 second/forced vital capacity (FEV1 /FVC) ratio than previous and current smokers (P < 0.001). The FEV1 /FVC ratio declined faster in current smokers than in never smokers (P = 0.05) or ex-smokers (P = 0.01). The baseline modified Rodnan skin thickness score (MRSS) and the MRSS decline were comparable across smoking groups. Although heavy smoking (>25 pack-years) increased the odds of digital ulcers by almost 50%, there was no robust adverse association of smoking with digital ulcer development. CONCLUSION: The known adverse effect of smoking on bronchial airways and alveoli is also observed in SSc patients; however, robust adverse effects of smoking on the progression of SSc-specific pulmonary or cutaneous manifestations were not observed.

3.
Rheumatol Int ; 37(7): 1195-1202, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28516236

RESUMO

The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective study, was primarily designed to assess the percentage of patients [aged ≥18 years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence to prescribed subcutaneous biologicals. This paper reports data for the secondary objective from a subset of patients, namely to evaluate non-adherence to prescribed oral antirheumatic drugs in RA patients in Spain using the validated Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky-Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire, and a questionnaire (developed and validated in Spain) on patient satisfaction with RA treatment and preferences. A total of 271 patients (76.7% females; mean age 55.6 years) were being treated with oral drugs for RA, of which 234 completed the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The proportion of non-adherence in younger patients (aged ≤48 years; 37.5%) was double that recorded in patients aged >48 years (p = 0.006). Patients with a perception of lower efficacy also had a higher risk of non-adherence (p = 0.012). Multivariable analysis showed that younger age and male gender were independently associated with risk of non-adherence. There was only slight agreement between the CQR and Morisky-Green assessment tools (kappa coefficient = 0.186), possibly reflecting the fact that both questionnaires measure slightly different aspects of medication adherence. In conclusion, one out of five RA patients was identified as at risk for non-adherence with the CQR, and this was more frequent in younger patients and in males.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Adesão à Medicação , Inquéritos e Questionários , Administração Oral , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/psicologia , Distribuição de Qui-Quadrado , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Espanha , Resultado do Tratamento
4.
Sci Rep ; 7: 40303, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28059143

RESUMO

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.


Assuntos
Artrite Reumatoide/genética , Aterosclerose/complicações , Aterosclerose/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha
5.
Sci Rep ; 6: 31979, 2016 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27534721

RESUMO

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Aterosclerose/sangue , Aterosclerose/genética , Proteína C-Reativa/genética , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Idoso , Artrite Reumatoide/epidemiologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
6.
Arthritis Rheumatol ; 68(9): 2338-44, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27111665

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy. METHODS: The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. RESULTS: This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10(-6) ) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10(-12) ). Analysis of the biologic relevance of the known SSc-RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors. CONCLUSION: This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.


Assuntos
Artrite Reumatoide/genética , Estudo de Associação Genômica Ampla , Fatores Reguladores de Interferon/genética , Escleroderma Sistêmico/genética , Loci Gênicos , Predisposição Genética para Doença , Humanos , Fatores de Risco
7.
Medicine (Baltimore) ; 95(9): e2891, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26945378

RESUMO

The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ±â€Š12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81-3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0.001), and responded better to specific treatments for LN (P = 0.014). More than two-thirds of the patients with LN from a wide European cohort achieved a complete response to treatment. The presence of positive anti-Sm antibodies was associated with a higher frequency of LN and a decreased rate of complete response to treatment. The use of antimalarials reduced both the risk of developing renal disease and its severity, and contributed to attaining a complete renal response.


Assuntos
Nefrite Lúpica/epidemiologia , Sistema de Registros , Adolescente , Adulto , Feminino , Humanos , Nefrite Lúpica/terapia , Masculino , Recidiva , Estudos Retrospectivos , Reumatologia , Espanha/epidemiologia , Adulto Jovem
8.
PLoS One ; 10(11): e0143153, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26571131

RESUMO

OBJECTIVES: To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). RESULTS: RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. CONCLUSIONS: In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.


Assuntos
Artrite Reumatoide/genética , Aterosclerose/genética , Interleucina-33/genética , Adulto , Idoso , Alelos , Artrite Reumatoide/complicações , Aterosclerose/etiologia , Artérias Carótidas/diagnóstico por imagem , Feminino , Seguimentos , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Interleucina-1/genética , Risco , Ultrassonografia
9.
Arthritis Res Ther ; 17: 63, 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25885039

RESUMO

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.


Assuntos
Adalimumab/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Imunoglobulina G/genética , Infliximab/genética , Adalimumab/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Sequência de Bases , Feminino , Genótipo , Humanos , Alótipos de Imunoglobulina , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
10.
Pharmacogenet Genomics ; 24(1): 1-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24253594

RESUMO

BACKGROUND: The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA. MATERIALS AND METHODS: Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion. RESULTS: The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months). CONCLUSION: Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Interleucina-6/genética , Regiões Promotoras Genéticas , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/administração & dosagem , Artrite Reumatoide/genética , Citosina , Etanercepte , Feminino , Marcadores Genéticos , Genótipo , Guanina , Humanos , Imunoglobulina G/administração & dosagem , Infliximab , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores do Fator de Necrose Tumoral/administração & dosagem , Reprodutibilidade dos Testes , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA