Resumen
Antecedentes: Se ha sugerido que el vasoespasmo podría tener participación en el infarto agudo de miocardio (IAM). Existen tres subtipos de adrenorreceptores α2 en los seres humanos, conocidos como α2A-AR, α2B-AR y α2C-AR. Los α2-AR median la vasoconstricción coronaria en los seres humanos, y algunos estudios en ratones knockout (carentes del subtipo α2B-AR) sugieren el compromiso de este subtipo en la vasoconstricción. Una variante por deleción del gen humano α2B-AR se asocia con desensibilización disminuida del receptor in vitro. Previamente demostramos que los hombres portadores de dos alelos supresión del gen α2B-AR tienen riesgo incrementado de sufrir IAM. En el presente estudio, buscamos corroborar la asociación entre el genotipo deleción/deleción y el IAM, y estudiar si este genotipo también confiere un riesgo aumentado de muerte súbita de origen cardíaco (MSC). Métodos y resultados: Estudiamos una serie de 700 muertes súbitas, ocurridas fuera del ámbito hospitalario, en hombres de raza blanca de mediana edad y en quienes se había realizado la autopsia médico-legal; encontramos que los portadores del genotipo deleción/deleción tenían un riesgo incrementado de MSC (n = 278, OR = 2.0, p = 0.01) e IAM fatal (n = 84, OR = 2.1, p = 0.04) comparados con los otros dos genotipos combinados. El riesgo de MSC e IAM fatal fue mayor para los portadores del genotipo DD que fallecieron antes de los 55 años (OR = 4.5 y 5.0, p < 0.001 para ambos). Conclusiones: Concluimos que los hombres de raza blanca de edad mediana portadores del genotipo α2B-AR deleción/deleción, tienen riesgo significativamente incrementado de MSC e IAM, especialmente antes de los 55 años.
Palabras clave
Receptores adrenérgicos α2, polimorfismo genético, autopsia, muerte súbita de origen cardíaco, infarto de miocardio
Clasificación en siicsalud
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Especialidades
Principal: Cardiología
Relacionadas: Diagnóstico por Laboratorio, Medicina Interna, Medicina Interna
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Snapir, Amir,
Patrocinio y reconocimiento
La figura 1 fue publicada en Journal of American College of Cardiology, Snapir et al, 41(2):190-194, © (2003) y se reproduce con permiso del editor.
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INVOLVEMENT OF A GENETIC VARIATION IN THE ALPHA2B-ADRENOCEPTOR IN ACUTE CORONARY EVENTS AND SUDDEN CARDIAC DEATH
Abstract
Background: Vasospasm has been suggested to play a role in acute myocardial infarction (AMI). There are three subtypes of α2-adrenoceptors in humans, known as α2A-AR, α2B-AR, and α2C-AR. α2-ARs mediate coronary vasoconstriction in humans, and studies on knockout mice suggest the involvement of the α2B-AR subtype in vasoconstriction. A deletion variant of the human α2B-AR gene has been associated with impaired receptor desensitization in vitro. We have previously shown that men carrying two α2B-AR deletion alleles are at increased risk for AMI. In the current study we sought to corroborate the association between the deletion/deletion genotype and AMI, and to study whether this genotype also confers increased risk for sudden cardiac death (SCD). Methods and results: We studied a series of 700 sudden out-of-hospital deaths of middle-aged Caucasian men subjected to medico-legal autopsy, and found that carriers of the deletion/deletion genotype had an increased risk for SCD (n = 278, OR = 2.0, p = 0.01) and fatal AMI (n = 84, OR = 2.1, p = 0.04) compared with the other two genotypes combined. The risks for SCD and fatal AMI were higher in carriers of the DD genotype who died before the age of 55 (OR = 4.5 and 5.0, p < 0.001 for both). Conclusions: We conclude that middle-aged Caucasian men carrying the deletion/deletion genotype of the α2B-AR have a significantly increased risk for SCD and AMI, especially before the age of 55.
Key words
Receptors, adrenergic, α2, polymorphism genetics, autopsy, death sudden cardiac, myocardial infarction
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Bibliografía del artículo
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