RESUMEN
Most sequence variants identified hitherto in genome-wide association studies (GWAS) of atrial fibrillation are common, non-coding variants associated with risk through unknown mechanisms. We performed a meta-analysis of GWAS of atrial fibrillation among 29,502 cases and 767,760 controls from Iceland and the UK Biobank with follow-up in samples from Norway and the US, focusing on low-frequency coding and splice variants aiming to identify causal genes. We observe associations with one missense (OR = 1.20) and one splice-donor variant (OR = 1.50) in RPL3L, the first ribosomal gene implicated in atrial fibrillation to our knowledge. Analysis of 167 RNA samples from the right atrium reveals that the splice-donor variant in RPL3L results in exon skipping. We also observe an association with a missense variant in MYZAP (OR = 1.38), encoding a component of the intercalated discs of cardiomyocytes. Both discoveries emphasize the close relationship between the mechanical and electrical function of the heart.
RESUMEN
A sinus of Valsalva aneurysm is defined as a dilatation of the aortic sinuses, between the aortic valve annulus and the sinotubular junction. They are rare and most frequently involve the right coronary sinus. We report a case of an unruptured giant sinus of Valsalva aneurysm in a patient associated with ectasia of the left main stem and left anterior descending coronary artery. The patient was successfully treated with aortic root replacement using a biologic conduit.
Asunto(s)
Aneurisma de la Aorta/diagnóstico , Bioprótesis , Implantación de Prótesis Vascular/métodos , Enfermedad Coronaria/diagnóstico , Seno Aórtico/cirugía , Anciano , Aneurisma de la Aorta/complicaciones , Aneurisma de la Aorta/cirugía , Angiografía Coronaria/métodos , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/cirugía , Dilatación Patológica/complicaciones , Dilatación Patológica/diagnóstico , Dilatación Patológica/cirugía , Ecocardiografía Doppler/métodos , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Radiografía Torácica/métodos , Enfermedades Raras , Medición de Riesgo , Índice de Severidad de la Enfermedad , Seno Aórtico/diagnóstico por imagen , Seno Aórtico/patología , Resultado del TratamientoRESUMEN
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF. Mutations in potassium-channel genes have been associated with familial AF but account for only a small fraction of all cases of AF. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart.