The Genetic Basis of Atrial Fibrillation

The Genetic Basis of Atrial Fibrillation (AF)

Sponsors

Lead sponsor: University of Pittsburgh

Collaborator: EP Research funds

Source University of Pittsburgh
Brief Summary

The investigators' 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.

Detailed Description

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.

Overall Status Completed
Start Date January 2005
Completion Date January 2010
Primary Completion Date January 2010
Study Type Observational
Enrollment 50
Condition
Eligibility

Sampling method: Non-Probability Sample

Criteria:

Inclusion Criteria:

- 18+ years of age

- Able to give informed consent

Exclusion Criteria:

- Inability to provide informed consent

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
David S. Schwartzman, MD Principal Investigator University of Pittsburgh/UPMC
Location
facility University of Pittsburgh Medical Center/Comprehensive Heart Ctr.
Location Countries

United States

Verification Date

January 2016

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Arm group label: 1

Description: Patients of the Cardiovascular Institute with known cardiac conditions and no history of atrial fibrillation.

Arm group label: 2

Description: Patients of the Cardiovascular Institute with known cardiac conditions and a history of atrial fibrillation.

Study Design Info

Observational model: Case Control

Time perspective: Cross-Sectional

Source: ClinicalTrials.gov