RESUMO
No disponible
Assuntos
Humanos , Masculino , Adulto , Artéria Braquial/lesões , Artéria Braquial/cirurgia , Cateterismo Periférico , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/patologiaRESUMO
No disponible
Assuntos
Humanos , Feminino , Idoso de 80 Anos ou mais , Prótese de Quadril , Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Cimentos Ósseos/efeitos adversos , Ecocardiografia/métodos , Ecocardiografia , Embolia Pulmonar/complicações , Embolia Pulmonar , Tromboembolia/induzido quimicamente , Tromboembolia/complicaçõesAssuntos
Endocardite Bacteriana/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus , Idoso , Idoso de 80 Anos ou mais , Endocardite Bacteriana/diagnóstico , Humanos , Masculino , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Streptococcus/isolamento & purificaçãoRESUMO
OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.
Assuntos
Angiopoietina-2/sangue , Anticorpos Monoclonais , Aterosclerose , Osteopontina/sangue , Espondilite Anquilosante , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Infliximab , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Fatores de Risco , Espanha , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismo , Estatística como Assunto , Resultado do TratamentoRESUMO
OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.
Assuntos
Anticorpos Monoclonais , Gelsolina/metabolismo , Espondilite Anquilosante , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adipocinas/metabolismo , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Humanos , Inflamação/tratamento farmacológico , Infliximab , Infusões Intravenosas , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Gravidade do Paciente , Fatores Sexuais , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismo , Espondilite Anquilosante/fisiopatologia , Estatística como Assunto , Resultado do TratamentoRESUMO
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.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Cromossomos Humanos Par 11/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/genética , Demografia , Feminino , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoAssuntos
Aneurisma Aórtico/epidemiologia , Arteriopatias Oclusivas/epidemiologia , Biópsia , Doença da Artéria Coronariana/epidemiologia , Arterite de Células Gigantes/epidemiologia , Trombose/epidemiologia , Aneurisma Aórtico/mortalidade , Arteriopatias Oclusivas/mortalidade , Doença da Artéria Coronariana/mortalidade , Arterite de Células Gigantes/mortalidade , Arterite de Células Gigantes/patologia , Humanos , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Trombose/mortalidadeRESUMO
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.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Doenças Cardiovasculares/genética , Loci Gênicos/genética , Predisposição Genética para Doença , Adulto , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Artérias Carótidas/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , EspanhaRESUMO
La psoriasis y la artritis psoriásica se asocian con un mayor riesgo de eventos cardiovasculares y de mortalidad cardiovascular. Además de los factores clásicos de aterosclerosis, la gravedad de la afección cutánea influye en el aumento del riesgo cardiovascular en estos pacientes. En ambos procesos se observa la presencia de disfunción endotelial y un grosor aumentado de la íntima-media de la arteria carótida, como expresión de enfermedad cardiovascular subclínica. El tratamiento activo de la enfermedad y el manejo de los factores de riesgo cardiovascular clásicos son fundamentales para disminuir la morbilidad cardiovascular en estos pacientes. El establecimiento de guías clínicas para el manejo del riesgo cardiovascular abrirá, en el futuro, un nuevo abordaje clínico integral del paciente con psoriasis y la artritis psoriásica (AU)
Psoriasis and psoriatic arthritis are associated with increased risk of cardiovascular events and cardiovascular mortality. Alongside classic risk factors such as atherosclerosis, the severity of psoriatic skin disease also influences cardiovascular risk in these patients. In both cases, endothelial dysfunction and increased intima-media thickness in the carotid artery are indicators of subclinical cardiovascular disease. Active treatment of the psoriasis and management of traditional cardiovascular risk factors are essential in order to reduce cardiovascular morbidity in these patients. Clinical practice guidelines on the management of cardiovascular risk will define a new integrated approach to the care of patients with psoriasis and psoriatic arthritis (AU)
Assuntos
Humanos , Masculino , Feminino , Artrite Psoriásica , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/mortalidade , Artrite Psoriásica/prevenção & controle , Artrite Psoriásica/terapia , Doenças Cardiovasculares , Doenças Cardiovasculares/mortalidade , Aterosclerose , Gerenciamento Clínico , Fatores de Risco , Artrite ReumatoideRESUMO
To further investigate into the epidaemiology of systemic lupus erythematosus (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and survival of patients diagnosed with late-onset SLE (age ≥ 50 years) according to the 1982 American College of Rheumatology (ACR) classification criteria at the single hospital for a well-defined population of Lugo, Northwestern (NW) Spain. Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed as having SLE fulfilled definitions for late-onset SLE. The predominance of women among late-onset SLE (4:1) was reduced when compared with that observed in early-onset SLE (7:1). However, the incidence of late-onset SLE was significantly higher in women (4.2 [95% confidence interval (CI): 3.1-5.6] per 100,000 population) than in men (1.3 [95% CI: 0.6-2.2] per 100,000 population) (p < 0.001). As observed in early-onset SLE, the most frequent clinical manifestation in patients with late-onset SLE was arthritis (71.2%). Renal disease was less common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In contrast, secondary Sjögren syndrome was more commonly found in the older age-group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p = 0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were significantly less common in late-onset SLE patients than in early-onset SLE. The probability of survival was reduced in late-onset SLE (p < 0.001). With respect to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE, respectively. In conclusion, our results confirm that in NW Spain SLE is not uncommon in individuals 50 years and older. In keeping with earlier studies, late-onset SLE patients from NW Spain have some clinical and laboratory differences with respect to those individuals with early-onset SLE. Our data support the claim of a reduced probability of survival in the older age-group of SLE patients.
Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Idade de Início , Idoso , Anticorpos Antinucleares/sangue , Feminino , Humanos , Incidência , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologia , Adulto JovemRESUMO
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.
Assuntos
Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Predisposição Genética para Doença , Metionina Sulfóxido Redutases/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Epitopos/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Psoriasis and psoriatic arthritis are associated with increased risk of cardiovascular events and cardiovascular mortality. Alongside classic risk factors such as atherosclerosis, the severity of psoriatic skin disease also influences cardiovascular risk in these patients. In both cases, endothelial dysfunction and increased intima-media thickness in the carotid artery are indicators of subclinical cardiovascular disease. Active treatment of the psoriasis and management of traditional cardiovascular risk factors are essential in order to reduce cardiovascular morbidity in these patients. Clinical practice guidelines on the management of cardiovascular risk will define a new integrated approach to the care of patients with psoriasis and psoriatic arthritis.
Assuntos
Doenças Cardiovasculares/etiologia , Psoríase/complicações , Artrite Psoriásica/complicações , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Comorbidade , Diabetes Mellitus/epidemiologia , Suscetibilidade a Doenças , Dislipidemias/epidemiologia , Endotélio Vascular/fisiopatologia , Humanos , Inflamação/etiologia , Obesidade/epidemiologia , Guias de Prática Clínica como Assunto , Psoríase/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologiaRESUMO
Objetivo Actualmente existen seis estatinas comercializadas en España y una en proceso de comercialización. La elección de la más adecuada y de su dosis habitualmente viene determinada por el objetivo terapéutico; es decir, en el descenso de c-LDL. Se aceptan como dosis equivalentes de las distintas estatinas aquellas que consiguen el mismo porcentaje de descenso en c-LDL, sin embargo, se trata de fármacos que difieren no sólo en su potencia, sino también en sus propiedades farmacocinéticas. Una evaluación de las peculiaridades farmacocinéticas de cada estatina permite disponer de criterios para su elección, ayudando a determinar qué estatina puede ser más apropiada para un paciente en función de sus características individuales y de los medicamentos que son coadministrados. Métodos Se revisaron las características farmacocinéticas de cada estatina y las interacciones medicamentosas que de ello se derivan. Resultados El CYP3A4 es responsable del metabolismo de atorvastatina, simvastatina y lovastatina; el CYP2C9 de fluvastatina; la P-gp favorece la eliminación de atorvastina, pravastatina, simvastatina y lovastatina; y la actividad del transportador OATP1B1, que favorece el acceso al hepatocito de todas las estatinas excepto fluvastatina, es especialmente importante con rosuvastatina y pravastatina. Estas circunstancias son responsables de que aquellos fármacos que afectan a la actividad de estos isoenzimas o transportadores, bien por inhibición bien por inducción, no afecten por igual a la actividad de las diferentes estatinas. Conclusión A la hora de seleccionar una estatina o de intercambiar una por otra, deben tomarse en consideración las características farmacocinéticas de cada una de ellas(AU)
Objective The pharmaceutical industry currently offers six different statins in Spain and there is one more soon to be available. Choosing the most appropriate drug and dose is determined by the therapeutic target (reduction in LDL-C levels). Statin doses that decrease LDL-C at the same percentage are considered equivalent. Evaluating the pharmacokinetic characteristics of each statin can be useful when setting selection criteria, helping to determine which statin may be more appropriate for a patient based on their individual characteristics and on the other co-administered drugs. Methods We reviewed the pharmacokinetics properties of each statin and its possible involvement in drug interactions.ResultsCYP3A4 was responsible for the metabolism of lovastatin, simvastatin and atorvastatin; fluvastatin depends on CYP2C9; P-glycoprotein is responsible for decreased atorvastatin, pravastatin, simvastatin and lovastatin concentrations. The OATPA1B1 transporter involved in all statins access to the hepatocyte, except for fluvastatin, is essential for rosuvastatin and pravastatin. These circumstances cause those drugs inhibiting or inducing isoenzymes or transporters activity not to have the same effect on the different statins. Conclusion The pharmacokinetics is important when choosing the best statin and could be a limitation in the use of interchange therapeutic programmes when other drugs are present (AU)
Assuntos
Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Intercambialidade de Medicamentos , Uso de Medicamentos/estatística & dados numéricos , Sinvastatina/farmacocinética , Interações Medicamentosas , Lovastatina/farmacocinéticaRESUMO
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.
Assuntos
Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Transativadores/genética , Adulto , Idoso , Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: The pharmaceutical industry currently offers six different statins in Spain and there is one more soon to be available. Choosing the most appropriate drug and dose is determined by the therapeutic target (reduction in LDL-C levels). Statin doses that decrease LDL-C at the same percentage are considered equivalent. Evaluating the pharmacokinetic characteristics of each statin can be useful when setting selection criteria, helping to determine which statin may be more appropriate for a patient based on their individual characteristics and on the other co-administered drugs. METHODS: We reviewed the pharmacokinetics properties of each statin and its possible involvement in drug interactions. RESULTS: CYP3A4 was responsible for the metabolism of lovastatin, simvastatin and atorvastatin; fluvastatin depends on CYP2C9; P-glycoprotein is responsible for decreased atorvastatin, pravastatin, simvastatin and lovastatin concentrations. The OATPA1B1 transporter involved in all statins' access to the hepatocyte, except for fluvastatin, is essential for rosuvastatin and pravastatin. These circumstances cause those drugs inhibiting or inducing isoenzymes or transporters' activity not to have the same effect on the different statins. CONCLUSION: The pharmacokinetics is important when choosing the best statin and could be a limitation in the use of interchange therapeutic programmes when other drugs are present.
Assuntos
Anticolesterolemiantes/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacocinética , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP2C9 , Indústria Farmacêutica , Interações Medicamentosas , Prescrições de Medicamentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Fígado/metabolismo , Transportador 1 de Ânion Orgânico Específico do Fígado , Transportadores de Ânions Orgânicos/metabolismo , EspanhaRESUMO
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.
Assuntos
Artrite Reumatoide/genética , Aterosclerose/genética , Receptor gp130 de Citocina/genética , Polimorfismo Genético , Receptores de Interleucina-6/genética , Adulto , Alelos , Artrite Reumatoide/complicações , Aterosclerose/complicações , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , EspanhaRESUMO
OBJECTIVES: Visfatin is an adipokine encoded by the NAMPT (PBEF1) gene. In this study we assessed the potential association of two NAMPT gene polymorphisms with disease susceptibility and cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). METHODS: A total of 1,395 patients fulfilling the 1987 ACR classification criteria for RA and 1,230 matched controls, were genotyped for the NAMPT rs9770242 and rs59744560 gene polymorphisms, located within the proximal promoter, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. In a second step, 1,196 patients in whom full information was available were assessed to determine the influence of NAMPT rs9770242 and rs59744560 polymorphisms in the development of CV events. Also, the potential influence of these polymorphisms in the development of subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=125) and by B-mode ultrasonography to determine the carotid artery intima-media thickness (n=105). RESULTS: No statistically significant differences in the allele or genotype frequencies for the NAMPT gene polymorphisms between RA patients and controls were found. A modest non significant lower frequency of the minor allele G of rs9770242 polymorphism was observed among patients with CV disease (20.62%) compared to those without CV disease (22.83%) (p=0.39). Also, a slight nonsignificant lower frequency of the minor allele T of rs59744560 polymorphism in patients with CV events (9.81%) compared with those RA patients who did not experience CV disease (13.07%) (p=0.11) was observed. Likewise, no significant association between the NAMPT polymorphisms with surrogate markers of subclinical atherosclerosis was found in patients with RA. CONCLUSIONS: NAMPT rs9770242 and rs59744560 polymorphisms are not markers of disease susceptibility and CV disease in RA.
Assuntos
Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Citocinas/genética , Nicotinamida Fosforribosiltransferase/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Análise de Variância , Artrite Reumatoide/complicações , Artrite Reumatoide/enzimologia , Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Regiões Promotoras Genéticas , Medição de Risco , Fatores de Risco , Espanha , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia , VasodilataçãoRESUMO
OBJECTIVES: To assess the potential association between LEP rs2167270 (19 G>A) gene polymorphism and disease susceptibility and cardiovascular disease (CV) in patients with rheumatoid arthritis (RA). METHODS: 773 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, Spain, and 957 matched controls, were studied. Patients were genotyped for the LEP rs2167270 (19G>A) polymorphism, located within the 5´UTR, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=133) and by B-mode ultrasonography of the carotid artery intima-media thickness (n=113). RESULTS: No statistically significant differences in the genotype or allele frequencies of the LEP rs2167270 gene polymorphism between patients with RA and controls were seen. Likewise, LEP rs2167270 polymorphism did not influence the development of CV events. Also, no significant differences in LEP rs2167270 genotype or allele distribution were seen when results of surrogate markers of subclinical atherosclerosis were assessed. CONCLUSIONS: LEP rs2167270 polymorphism does not seem to be a genetic risk factor for disease susceptibility or clinically evident CV disease and subclinical atherosclerosis in patients with RA.