Gene linked to lone atrial fibrillation in younger patients

Gene linked to lone atrial fibrillation in younger patients

A common gene variant may increase the risk of lone atrial fibrillation (AF), a type of irregular heartbeat that is seen in younger patients who have no other symptoms heart disease, according to a new study from a team of international researchers.

A paper on the finding was published in the advance online issue of Nature Genetics on 21 February. The research team comprised members from the US, Switzerland, Germany, The Netherlands, Estonia and Iceland. The US National Institutes of Health and other public and private sponsors paid for the research.

One of the corresponding authors, Dr Patrick Ellinor, of the Massachusetts General Hospital (MGH) Cardiovascular Research Center and Cardiac Arrhythmia Service in Boston, who is also assistant professor of Medicine at Harvard Medical School, told the media that:

"The genetic location we have identified could be a new drug target for the treatment of AF."

"We also will be investigating whether these variants can help us predict patients' clinical outcomes or their response to the various treatments for AF," he added.

In their paper the researchers describe finding a protein that may help control the heart's electrical activity and thereby increase the risk of lone AF, a condition seen in younger patients with no other overt symptoms of heart disease.

AF, which affects more than 2.2 million people in the US, is the most common form of irregular heartbeat, of which there are several. It occurs when the upper chambers of the heart,the atria, which are controlled by electrical impulses, beat in a rapid and uncoordinated fashion.

The job of the atria is to pump blood into the lower chambers of the heart, the ventricles that pump the blood around the body and to the lungs. With AF, the ventricles receive the blood in a way that is out of step with their pumping rhythm. This causes blood to pool in the heart and increases the risk of a clot, which can then travel to the brain and cause a stroke.

Although AF is more common in older people with high blood pressure, heart failure and other forms of heart disease, about 10 per cent of patients start showing signs when they are younger and with no other symptoms of heart problems: this is known as lone AF.

Treatments for lone AF include blood-thinning drugs to prevent clots and other drugs to slow heart rhythm. If this does not work, there is also a minimally invasive surgical procedure called catheter ablation, where an electrophysiologist burns away the area of the atrial heart tissue that causes the erratic electrical signals.

There is evidence that a family history of AF can increase a person's risk of having it, and several studies have found links between gene variants on chromosomes 4 and 16 and increased risk.

However, in this case, Ellinor and colleagues focused on searching for gene variants that increased the risk of inheriting lone AF.

For the study, they carried out a meta-analysis of previous genome wide association (GWA) studies. A meta-analysis is a way of pooling and analyzing data from several studies as if they were one big study. To do this the studies must be of compatible design and there are strict criteria for inclusion and exclusion, for instance depending on sampling rules.

In this case the researchers found five previous GWA studies covering a total of 1,300 individuals with lone AF whose data they could included in a meta-analysis. One of the rules for inclusion was the definition of a person with AF, which they specified as an individual with no other signs of heart disease and whose symptoms began before they reached the age of 65.

The studies, which drew on cases in the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and the Massachusetts General Hospital, also contributed data on 13,000 unaffected participants for comparison.

The analysis showed that lone AF was linked to several common variants on a segment of chromosome 1, the most significant being in a gene for KCNN3, a potassium channel protein that carries signals across cell membranes in the brain, heart and other organs of the body.

We don't know exactly what the protein coded by KCNN3 does; the authors wrote that it "encodes a potassium channel protein involved in atrial repolarization", so it may reset the electrical signals in the atria. Animal studies on another potassium channel protein coded by KCNN2 suggests it helps controls signals from the atria and the pulmonary veins, both of which are involved in lone AF.

Ellinor and colleagues replicated their findings using a separate data pool comprising another 1,000 lone AF patients and 3,500 controls extracted from two other GWA studies.

They recommended further studies be done to clarify exactly how variants of KCNN3 and similar genes are linked to risk for lone AF. Also, these should investigate whether such genes would make useful drug targets and whether they could predict how a patient's symptoms might develop.

"Common variants in KCNN3 are associated with lone atrial fibrillation."

Patrick T Ellinor, Kathryn L Lunetta, Nicole L Glazer, Arne Pfeufer, Alvaro Alonso, Mina K Chung, Moritz F Sinner, Paul I W de Bakker, Martina Mueller, Steven A Lubitz, et al.

Nature Genetics, Advance online publication, 21 February 2010


Related article:

Atrial Fibrillation Treated Much More Successfully With Catheter Ablation Than Drugs.

Source: Massachusetts General Hospital.

The two types of Afib (Video Medical And Professional 2020).

Section Issues On Medicine: Cardiology