DNA sequence variations linked to electrical signal conduction in the heart

November 14, 2010, New York University School of Medicine

(PhysOrg.com) -- Scientists studying genetic data from nearly 50,000 people have uncovered several DNA sequence variations associated with the electrical impulses that make the heart beat. The findings, reported in Nature Genetics, may pave the way for a greater understanding of the mechanisms for abnormal heart rhythms and sudden cardiac death.

"Regulation of the heart's rhythm is exceedingly complex," says co-author Glenn I. Fishman, MD, the William Goldring Professor of Medicine and the director of the Leon H. Charney Division of at NYU Langone Medical Center. "This study provides new clues about the biologic pathways that influence cardiac conduction. Our hope is that this information will translate into novel approaches to prevent or treat serious rhythm disorders, including sudden cardiac death."

Normally, signals start from specialized called pacemaker cells, travel through the and cause rhythmical muscle contractions – a system called cardiac conduction. The signals register on heart monitors as the electrocardiogram, or ECG. Abnormalities in cardiac conduction, particularly in the ventricles of the heart, can be extremely dangerous, leading to which affects approximately 250,000 people each year in the United States. Treatment with a pacemaker or a specialized device known as an implantable defibrillator may be needed to regulate the heart's rhythm.

Researchers have known for some time that genetic factors contribute to electrical activity in the heart, including conduction of the electrical signal throughout the heart chambers. The new study reports on several previously unsuspected regions in the genome associated with cardiac electrical activity.

An international collaboration of scientists identified genetic associations with cardiac ventricular conduction in 22 regions of the genome in the largest study of its kind in conduction. The data was generated by an analysis of 15 European and American centers, representing nearly 50,000 individuals of European descent. Genome-wide association studies examine hundreds of thousands of genetic variants in thousands of people to try to find sequence variants and genes associated with particular diseases or conditions.

Some of these genetic variations were found in two sodium channel genes that sit side-by-side on the human genome. Sodium channels are molecular gated pores in living cells that control the flow of sodium ions – electrically charged particles – critical for the heart beat. The first gene, SCN5A, is well known to be involved in cardiac conduction. The second, SCN10A, has only recently been found in the heart.

As part of the study, Dr. Fishman and his team at NYU Langone identified where in the heart the SCN10A channels reside and discovered they were particularly abundant in specialized conduction fibers of the mouse heart key to the orderly contraction of the heart. The researchers then treated mice with a drug that selectively blocked this sodium channel and found that cardiac conduction was delayed, affecting the ECG. In addition to cardiac sodium channel genes, the study found that a number of other genes and genetic pathways involved in cardiac conduction, including calcium handling processes and transcription factors which influence cardiac development and formation. Dysfunctions in these processes before birth can lead to heart malformations in newborns.

Related Stories

Recommended for you

Add broken DNA repair to the list of inherited colorectal cancer risk factors

February 23, 2018
An analysis of nearly 3,800 colorectal cancer patients—the largest germline risk study for this cancer to date—reveals opportunities for improved risk screening and, possibly, treatment.

Team identifies genetic defect that may cause rare movement disorder

February 22, 2018
A Massachusetts General Hospital (MGH)-led research team has found that a defect in transcription of the TAF1 gene may be the cause of X-linked dystonia parkinsonism (XDP), a rare and severe neurodegenerative disease. The ...

Defects on regulators of disease-causing proteins can cause neurological disease

February 22, 2018
When the protein Ataxin1 accumulates in neurons it causes a neurological condition called spinocerebellar ataxia type 1 (SCA1), a disease characterized by progressive problems with balance. Ataxin1 accumulates because of ...

15 new genes identified that shape human faces

February 20, 2018
Researchers from KU Leuven (Belgium) and the universities of Pittsburgh, Stanford, and Penn State have identified 15 genes that determine facial features. The findings were published in Nature Genetics.

New algorithm can pinpoint mutations favored by natural selection in large sections of the human genome

February 20, 2018
A team of scientists has developed an algorithm that can accurately pinpoint, in large regions of the human genome, mutations favored by natural selection. The finding provides deeper insight into how evolution works, and ...

New software helps detect adaptive genetic mutations

February 20, 2018
Researchers from Brown University have developed a new method for sifting through genomic data in search of genetic variants that have helped populations adapt to their environments. The technique, dubbed SWIF(r), could be ...

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.