The Genetic Basis of Atrial Fibrillation (AF)

Atrial fibrillation (AF), a heart rhythm disorder, is a major health problem. As many as 3
million US persons are afflicted; this number is expected to rise significantly in coming
decades because AF incidence is directly correlated with age. AF is significantly associated
with cardiovascular morbidity and mortality.

Our goal with this research is to:

1. Establish a clinical database and a DNA bank for 1000 individuals with AF and 1000
individuals without AF.

2. Directly test the hypothesis that known functional polymorphisms in the coding
sequences and the promoter regions of cardiac genes (ion channels and genes known to
affect survival in the setting of left ventricular dysfunction) predispose individuals
to AF.

Over the past decade, advancing techniques and technologies for gene characterization have
yielded significant clues as to the molecular mechanism of certain human heart rhythm
disorders. The role of ion channel polymorphisms in subjects with AF is unknown. Similarly,
it is also not known whether polymorphisms in other genes have an impact on the risk of AF.

The ability to characterize genomic "at-risk" profiles would have many potential benefits
for patient care. Paramount among these is:

1. Increased oversight or intervention of at-risk subjects, which might prevent
unnecessary morbidity and mortality due to AF.

2. Further insight into the pathogenesis of AF, which may lead to preventative or curative
therapies.

Subjects will be recruited from the patient pool of the Cardiovascular Institute (including
the Comprehensive Heart Center and the PUH Outpatient Cardiology Clinic). For each subject
enrolled, we will record demographic information; etiology and details of heart disease;
family history of heart disease; non-cardiac medical history; physical exam findings;
medicinal therapy; and results of prior cardiac testing (such as echocardiograms [Echo],
gated blood pool scans of heart function [MUGAs], exercise stress tests [ESTs] cardiac
catheterizations, and clinical electrophysiology studies [EP Studies]. Records will be
maintained with identifiers in a locked file cabinet in the office of the Principal
Investigator.

A blood sample of ~10 ml will be drawn from each participating subject on the day of
enrollment. Blood samples will be drawn only once from each subject. There is no further
follow up required for the subject. Blood will be sent to the University of Pittsburgh
School of Medicine Cardiovascular Research Center where nucleated cells will be isolated
from whole blood by centrifugation. DNA will be isolated from nucleated cells and stored at
the Cardiovascular Research Center (on the 17th floor of the Biomedical Science Tower). All
DNA samples will be coded to ensure confidentiality, and maintained in a locked freezer for
the duration of the study (5 years). Samples will be destroyed if requested by the subject.
Samples (blood and DNA) will be under the control of the Principal Investigator. The DNA
samples will be used to identify polymorphisms in ion channel genes, as well as other genes
that may be associated with an increased risk of AF. Genotyping of polymorphisms will be
performed on the genomic DNA. The genomic DNA will be amplified by polymerase chain reaction
method using gene-specific primers. For each polymorphism, genotype will be identified. We
will determine the frequency of that genotype in our study population, and attempt to define
significant associations with AF.

Inclusion Criteria:

- 18+ years of age

- Able to give informed consent

Exclusion Criteria:

- Inability to provide informed consent