: The candidate has a basic science background in cellular physiology and has recently completed medical residency, cardiology and electrophysiology fellowship training. He is currently a clinical research fellow and will join the staff of the Cardiology Division at Massachusetts General Hospital in July 2002. The candidate seeks to obtain formal training in clinical research methods while developing a research program to elucidate the molecular basis of atrial fibrillation. Atrial fibrillation is the most common significant arrhythmia, affecting over 2 million Americans. Although rare in youth, the prevalence of atrial fibrillation increases with age and afflicts one in ten individuals over eighty. Atrial fibrillation presents a considerable socioeconomic burden, associated with chronic medication use, nearly one fourth of all strokes in the elderly, and a reduced life expectancy in affected individuals. Most atrial fibrillation is considered secondary to other conditions such as hyperthyroidism, hypertension, cardiomyopathy or valvular disorder; however, a substantial minority of patients without obvious cause are said to have """"""""!one"""""""" atrial fibrillation. The clinical heterogeneity of atrial fibrillation has restricted previous attempts to define the genetic etiology of this disorder. We therefore propose use of a complementary strategy of individuals and families to further define the clinical phenotypes, the genetic epidemiology, and the genetic basis of this disorder. Of patients with atrial fibrillation, we hypothesize that individuals with lone atrial fibrillation are the most likely to have a genetic component to their condition. We propose to prospectively study these individuals and their first-degree relatives in order to formally define the genetic architecture of atrial fibrillation while identifying larger kindreds suitable for positional cloning approaches. With this approach, we have characterized over one hundred probands with lone atrial fibrillation and identified multiple extended families with inherited atrial fibrillation. Further efforts to identify the causal genes are underway. Identification of these genes will permit definition of the molecular pathways that contribute to atrial fibrillation, while the availability of the probands will enable longitudinal studies using genotypes to predict outcomes and enable detailed evaluation of gene-gene and gene-drug interactions. The ultimate goal of these complementary strategies is to lead to novel therapeutic strategies for the prevention and treatment of this common and morbid condition.
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| Albert, Christine M; Nam, Edwin G; Rimm, Eric B et al. (2008) Cardiac sodium channel gene variants and sudden cardiac death in women. Circulation 117:16-23 |
| Ellinor, Patrick T; Yi, B Alexander; MacRae, Calum A (2008) Genetics of atrial fibrillation. Med Clin North Am 92:41-51, x |
| Darbar, Dawood (2006) Screening for genomic alterations in congenital long QT syndrome. Heart Rhythm 3:56-7 |
| Ho, Ivan C K; Milan, David J; Mansour, Moussa C et al. (2006) Fungal infection of implantable cardioverter-defibrillators: case series of five patients managed over 22 years. Heart Rhythm 3:919-23 |
| Milan, David J; Jones, Ian L; Ellinor, Patrick T et al. (2006) In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation. Am J Physiol Heart Circ Physiol 291:H269-73 |
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