Afib Answers
While atrial fibrillation is the most common cardiac arrhythmia, its causes are not fully known, and current treatment methods are only partly effective. Prof. Amos Katz, dean of the Faculty of Health Sciences at Ben-Gurion University, and his team have undertaken genetic studies of three generations of a Jewish family of Iranian descent to identify a previously unknown mechanism for the disease: a genetic mutation. It may enable the researchers to create a precision medicine based on the genetic findings.
“The mostly night-time atrial fibrillation was shown to be caused by a mutation in a gene (KCND2), encoding a crucial component of a potassium ion channel (Kv4.2) in the heart,” Katz said. The team is trying to find a workable therapy for atrial fibrillation (AF) that happens when someone is at rest, relaxation or sleep. Because of its specificity to the cardiac atria and its nighttime expression, this channel could be an optimal drug target for novel treatment modalities of atrial fibrillation.
Katz explained that AF is a type of arrhythmia or abnormal/irregular heart rhythm. Although arrhythmia can cause stroke or heart failure, the condition is not immediately life-threatening. It happens when electrical impulses fire off from different places in the top chambers of the heart (atria), in a disorganized fashion. This team’s findings represent the first time that nighttime atrial fibrillation has been associated with a gene.
Katz began to realize the genetic implications when he treated three generations of family members for night-time AF. While the condition normally tends to affect older people, family members as young as 20 were exhibiting signs of it. As he explained, “I saw that it was a situation of autosomal dominance. About 50 percent of the family members had the ailment.”
The gene was discovered by Max Drabkin, an MD-PhD student in Prof. Ohad Birk’s research group at the Morris Kahn Laboratory of Human Genetics at BGU, who demonstrated that the abnormal electrical activity linked to its mutation was a result of excessive activity of the ion channel encoded by the gene. As a result, the research team, within the National Institute for Biotechnology in the Negev (NIBN) and the Faculty of Health Sciences at BGU, is beginning to develop an anti-arrhythmia medication.
According to Birk, “Combining genetic studies with frog oocyte and mutant mouse analyses, our research group demonstrated that the mutation increases conductivity of the channel, thus greatly enhancing predilection to atrial fibrillation. This ion channel is unique in that it is expressed specifically in the cardiac atria and has circadian rhythm: It is expressed at significantly higher levels during the night-time, explaining why its mutation causes atrial fibrillation specifically at night.”
These findings, which were published in the cardiology journal, Circulation: Genomic and Precision Medicine, indicate that people who suffer from nighttime AF may be able to benefit from medications that are developed to treat people who carry a mutation in this gene, Katz concluded.
