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Tactless hearts

Gene variant promotes atrial fibrillation

Munich, 07/13/2009

A new genetic variant associated with increased susceptibility for atrial fibrillation (AF) has been identified in two large-scale international studies that included significant contributions from LMU Munich researchers. AF is a chronic disruption of the heart's rhythm that affects an estimated one million people in Germany alone and as many as 600 million people worldwide. This disorder occurs when the heart’s natural pacemaker, the sinus node, can no longer maintain its precise synchronization of the ventricles and atria in the heart. The result is erratic contractions. AF is not acutely life-threatening, but it can lead to stroke or heart failure. “The locus we have mapped to chromosome 16 can influence the risk of this disorder,” LMU medical scientist PD Dr. Stefan Kääb reports. “It affects the synthesis of an important molecule for the heart's development. We hope our results will provide new insights into the onset of the disorder, and ultimately yield therapeutic approaches as well.” The second study in which LMU researchers were involved, led by Professor Martin Dichgans, identified the same locus and a correlation with the occurrence of strokes. (Nature Genetics online, 13 July 2009)

A human heart will have to beat up to three billion times over a normal lifespan if it is to keep blood pumping ceaselessly through the body. To keep the blood flowing smoothly, the contractions of the atria and ventricles are kept in perfect synchrony. Responsible for this is the sinus node, a group of specialized cells in the right atrium that keeps the beat using electrical signals. If the sinus node can no longer do its task adequately, the heart’s rhythm becomes erratic.

Atrial fibrillation is one outcome that is not acutely dangerous, but which can result in life-threatening complications. Blood is no longer pumped completely out of the heart, and clots can form. If one of these clots escapes, it can block a blood vessel and cause an embolism or stroke. One in four people in America and Europe has a lifetime risk of developing AF. The first clues of a genetic susceptibility came from studies of families: direct relatives of AF patients are at higher risk of developing AF as well.

As participants in this genome-wide association study, Kääb and his fellow LMU Munich researchers worked alongside scientists of Helmholtz Zentrum München, TU München and 40 other European and American institutions. They identified genes associated with AF as well as their naturally occurring variants. Genes are segments of DNA that encode the blueprints for proteins. Data from more than 40,000 people of European descent was analyzed – and two and a half million common variants tested, with success: The researchers managed to identify an important new locus on chromosome 16.

The results have since been verified and confirmed in another 6,000 people. Kääb’s group organized this important patient population for the study. This is the second region in the human genome – after another, already known locus on chromosome 4 – found to be significant to the risk of atiral fibrillation. “This new locus, like the one on Chromosome 4, affects the synthesis of an important molecule for the heart's development,” Kääb explains. “We now need to characterize the function of the gene in question, in order to gain more insights into the onset of the disorder, and possibly develop new kinds of therapy.”

The project was funded, among others, by the German Federal Ministry for Education and Research (BMBF) through its AF network “Kompetenznetz Vorhofflimmern”, the German National Genome Research Network (NGFN), the LMU Investment Fund in the scope of the Excellence initiative and the “Fondation Leducq”. (suwe)



“Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry”
Emelia J. Benjamin et. al
DOI: 10.1038/ng.416

“A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke“
Daniel F. Gudbjartsson
DOI: 10.1038/ng.417

Nature Genetics online, 13 July 2009


Privatdozent Dr. Stefan Kääb
Klinikum der Universität München
Tel.: +49 (0) 89 / 7095-3049
Fax: +49 (0) 89 / 7095-6076

Professor Dr. Martin Dichgans
Klinikum der Universität München
Tel.: +49 (0) 89 / 7095-6670
Fax: +49 (0) 89 / 7095-6679

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