Assuntos
Proteínas ADAM/genética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Proteína Cofatora de Membrana/genética , Proteínas ADAM/imunologia , Proteína ADAMTS13 , Adulto , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/imunologia , Sequência de Bases , Criança , Via Alternativa do Complemento/genética , Via Clássica do Complemento/genética , Diagnóstico Diferencial , Feminino , Expressão Gênica , Heterozigoto , Humanos , Masculino , Proteína Cofatora de Membrana/imunologia , Dados de Sequência Molecular , Mutação , Linhagem , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/genética , Púrpura Trombocitopênica Trombótica/imunologia , Fator de von Willebrand/genética , Fator de von Willebrand/imunologiaRESUMO
BACKGROUND: NPR3, located on human chromosome 5 (5p14-p13), encodes the natriuretic peptide receptor type C (NPR-C) that is mainly known as the natriuretic peptide clearance receptor. Involvement of NPR3 in susceptibility to cardiovascular diseases, i.e. hypertension, has been previously shown. With regard to stroke predisposition, evidence for a potential role of genetic variation within or nearby NPR3 has been suggested by a previous genome wide association study. METHODS: We investigated the contribution to early-onset ischemic stroke susceptibility of the NPR3 -55 C>A transition by genotyping this variant in an Italian cohort of 368 cases and 335 controls. RESULTS: In a multivariable logistic regression analysis adjusting for age, gender, hypertension, hypercholesterolemia, smoking habit and diabetes, a significant association of the -55 AA genotype with stroke was observed (OR=3.2, 95% CI 1.2-8.3, p=0.016). Remarkably, the polymorphism remained associated with stroke after adjusting for hypertensive status. CONCLUSION: Our observation obtained in an Italian cohort of early onset ischemic strokes suggests that a NPR3 promoter gene variant could have a role on cerebrovascular disease susceptibility.
Assuntos
Isquemia Encefálica/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Receptores do Fator Natriurético Atrial/genética , Acidente Vascular Cerebral/genética , Adulto , Idade de Início , Isquemia Encefálica/complicações , Feminino , Humanos , Itália , Masculino , Acidente Vascular Cerebral/etiologiaRESUMO
Atherothrombotic diseases are complex diseases, arising from the interaction between several genetic and environmental factors. Until recently, the genetic basis of complex diseases in general, and of atherothrombosis in particular, were poorly characterized. Progress in DNA analysis techniques and the increasing level of characterization of the variability of the human genome has recently allowed to study comprehensively the association between genetic variants and diseases. To date, more than 400 genome-wide association studies have been conducted, allowing to identify more than 430 genomic regions at which common genetic variants influence the predisposition to complex diseases of great epidemiological relevance. This review article summarizes the progress achieved in the genetic basis of atherothrombotic diseases such as myocardial infarction and ischemic stroke. The advances achieved so far now await for clinical applications.