RESUMEN
Mastocytosis is a rare disease with reported high interleukin-6 (IL6) levels influencing disease severity. The present study investigated polymorphisms within the genes that encode IL6 and its receptor (IL6R) in relation to mastocytosis development in a case-control design. Analysis of the IL6R Asp358Ala polymorphism showed that carriers of the AA genotype had a 2·5-fold lower risk for mastocytosis than those with the AC or CC genotypes. No association with mastocytosis was found for the IL6-174G/C polymorphism, however, it may influence the effect of IL6R polymorphism. To the best of our knowledge this is the first study analysing IL6/IL6R polymorphisms in mastocytosis.
Asunto(s)
Interleucina-6/genética , Mastocitosis/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-6/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Austria/epidemiología , Estudios de Casos y Controles , Epistasis Genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hungría/epidemiología , Leucemia de Mastocitos/genética , Masculino , Mastocitosis/epidemiología , Persona de Mediana Edad , Polonia/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Recently we found that the incidence of restenosis after carotid endarterectomy was significantly higher in patients homozygous for the normal genotype of mannose-binding lectin (MBL2) than in with patients with MBL2 variant genotypes. Several growth factors are also known to contribute to restenosis. Therefore, we investigated whether early postoperative changes in serum vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) concentrations and MBL2 genotypes interact in the development of restenosis. METHODS: Eighty-two patients who underwent carotid eversion endarterectomy and were followed up by carotid duplex scan sonography for 14 months were studied. Growth factors were measured preoperatively and 4 days after surgery. RESULTS: Pronounced significant increases in both VEGF and PDGF predicted restenosis but only in patients who were homozygous for the normal MBL2 genotype. In this group, the adjusted odds ratios of restenosis at 14 months in patients with high versus low early VEGF and PDGF increases were 27.73 (2.42 to 317.26) and 9.23 (1.45 to 58.70), respectively. CONCLUSIONS: These findings indicate that the development of restenosis depends on both complement activation regulated by the MBL2 gene and pathologic processes leading to enhanced production of VEGF and PDGF during the very early postoperative period.
Asunto(s)
Arterias Carótidas/fisiopatología , Estenosis Carotídea/sangre , Estenosis Carotídea/genética , Lectina de Unión a Manosa/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Anciano , Arterias Carótidas/patología , Arterias Carótidas/cirugía , Estenosis Carotídea/cirugía , Proteínas del Sistema Complemento/metabolismo , Análisis Mutacional de ADN , Endarterectomía Carotidea/estadística & datos numéricos , Factor de Crecimiento Epidérmico/sangre , Femenino , Marcadores Genéticos/fisiología , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Genotipo , Oclusión de Injerto Vascular/sangre , Oclusión de Injerto Vascular/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Regulación hacia Arriba/fisiologíaRESUMEN
Atherosclerosis is an inflammatory disease. The complement system plays an important role in the atherosclerotic process. However, lesser data is available on the possible role of C3 as a risk factor for atherosclerosis. Therefore, in a follow up study we determined C3 levels in 266 patients with pre-existing severe coronary artery disease (CAD) and compared their serum C3 concentrations with the cause of the disease. We investigated whether C3 levels predict the major complications of severe CAD during a 5-year long follow up period in patients, who have received an aorto-coronary bypass graft surgery. C3 concentrations were elevated in the patients with severe CAD compared to 182 healthy controls, and women had higher C3 concentrations than men. Pathological C3 levels (C3> or =1.8 g/L) were able to predict major complications of atherosclerosis (death by cardiac events, new acute myocardial infarction, stroke, carotid surgery and peripheral arterial disease) that developed during the follow up period only in women (OR: 4.1, 95% C.I. 1.23-13.61, p = 0.0249) independent of other risk factors for atherosclerosis. Our data supports the assumption that high C3 indicates the progression of atherosclerosis as a special marker of chronic inflammation.