Study finds specific genetic cue for sudden cardiac death syndrome

February 18, 2014

UC Irvine researchers have found a specific genetic flaw that is connected to sudden death due to heart arrhythmia – a leading cause of mortality for adults around the world.

While a number of genes have been linked with arrhythmias, UC Irvine's Geoffrey Abbott and his colleagues discovered that the of a gene called KCNE2 underlies a multisystem syndrome that affects both heart rhythm and blood flow and can activate chemical triggers that can cause sudden cardiac death.

"With these findings, we can now explore improved and for people who are at higher risk of sudden cardiac death, such as those with ," said Abbott, a professor of pharmacology and physiology & biophysics in the UC Irvine School of Medicine.

Study results appear in the February issue of Circulation: Cardiovascular Genetics, a publication of the American Heart Association.

Distinct from a heart attack, in which the heart continues to beat but is blocked, sudden cardiac death occurs when the heart ceases to beat because of the uncontrolled twitching of muscle fibers in its ventricles. Without defibrillation within minutes, this type of event is fatal.

In studies on a mouse model with the KCNE2 gene removed, Abbott and his colleagues had found catalysts for sudden cardiac death – including high blood cholesterol, anemia, high blood potassium, an age-related delay in the return to a resting position of the ventricle after contraction and, most surprisingly, diabetes.

Abbott said this link to diabetes and other systemic disturbances is significant because genes such as KCNE2 are better known for directly controlling the electrical signaling that ensures a steady heartbeat. The KCNE2 gene provides instructions for making a protein that regulates the activity of potassium channels, which play a key role in a cell's ability to generate and transmit electrical signals. Channels regulated by the KCNE2 protein are present in heart muscles and help recharge them after each heartbeat to maintain a regular rhythm.

In the current study, the researchers expanded on their previous work by showing that KCNE2 disruptions affect these rhythms in cardiac cells, which increases the risk of arrhythmia. Abbott said the major breakthrough in this study is that KCNE2 deletion could adversely affect so many other tissues outside the heart and that this dramatically worsened the outcome of cardiac electrical disturbances.

"Our discovery that a single gene disruption can give rise to a multitissue syndrome that predisposes one to challenges the established thinking that this type of genetic disruption can only give rise to a single component, such as abnormal electrical signaling in cardiac cells," Abbott said.

He pointed out that the use of full-gene knockout mice presents an exaggerated form of what occurs in human genetic syndromes.

"It's important to note that the mouse heart is very resistant to developing ventricular fibrillation," he said. "So the fact that we kept seeing this in the KCNE2-deleted mice gives us confidence that these findings are significant. We're currently using the same mouse model to investigate the mechanisms of myocardial infarction, another major cause of mortality recently associated with the KCNE2 gene."

The gene's relationship to diabetes is another area Abbott's group is exploring. He said that one of the potassium channels regulated by KCNE2 is strongly linked to human diabetes and is present in the islet cells of the pancreas, so one goal is to screen people with diabetes for DNA sequence variances in KCNE2.

Explore further: Unfolded protein response contributes to sudden death in heart failure

Related Stories

Unfolded protein response contributes to sudden death in heart failure

December 2, 2013
A researcher at the Cardiovascular Institute (CVI) at Rhode Island, The Miriam and Newport hospitals has found a link to human heart failure that if blocked, may reduce the risk of sudden cardiac death. The paper, written ...

New research takes aim at heart's 'safe zone'

October 28, 2013
Sudden cardiac arrest is the leading cause of death in the industrialized world. However, it's not well understood and is challenging to both predict and effectively prevent, according to Alain Karma, Arts and Sciences Distinguished ...

Estrogen levels tied to risk for sudden cardiac death in study

May 11, 2013
(HealthDay)—Higher levels of the hormone estrogen are associated with an increased risk of sudden cardiac death in men and women, a new study suggests.

Researchers discover how heart arrhythmia occurs

January 19, 2014
Researchers have discovered the fundamental biology of calcium waves in relation to heart arrhythmias.

Enzyme prevents fatal heart condition associated with athletes

May 25, 2011
Scientists have discovered an important enzyme molecule that may prevent fatal cardiac disorders associated with cardiac hypertrophy – the leading cause of sudden cardiac death in young athletes.

Recommended for you

How Gata4 helps mend a broken heart

August 15, 2017
During a heart attack, blood stops flowing into the heart; starved for oxygen, part of the heart muscle dies. The heart muscle does not regenerate; instead it replaces dead tissue with scars made of cells called fibroblasts ...

Injectable tissue patch could help repair damaged organs

August 14, 2017
A team of U of T Engineering researchers is mending broken hearts with an expanding tissue bandage a little smaller than a postage stamp.

Air pollution linked to cardiovascular disease; air purifiers may lessen impact

August 14, 2017
Exposure to high levels of air pollution increased stress hormone levels and negative metabolic changes in otherwise healthy, young adults in a recent study conducted in China. Air purifiers appeared to lessen the negative ...

Study hints at experimental therapy for heart fibrosis

August 14, 2017
Researchers report encouraging preclinical results as they pursue elusive therapeutic strategies to repair scarred and poorly functioning heart tissues after cardiac injury—describing an experimental molecular treatment ...

Scientists identify mutations in venous valve disease

August 14, 2017
A team of scientists has discovered that mutations in the genes FOXC2 and GJC2 are associated with defects in venous valves, flaps within veins that help maintain proper blood flow.

Mechanism behind sudden cardiac deaths in sports uncovered

August 10, 2017
Researchers have worked out the mechanism behind sudden cardiac deaths that follow a hard blow to the chest.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.