OTTAWA, June 22 /PRNewswire/ - Research at the University of OttawaHeart Institute has revealed that one of the most common forms of heartdisease - atrial fibrillation (AF) - is caused by a genetic mutation thatoccurs during in-utero development. The landmark discovery provides a freshview of how common diseases may develop and is expected to fuel targetedtherapies that help eliminate or prevent AF, which affects millions ofNorth Americans and is responsible for more than a third of all strokes. Details of the discovery are being reported in today’s issue of The NewEngland Journal of Medicine (vol. 354, No. 25, pp. 2637-2744,http://www.nejm.org). The work has been led by the Heart Institute’s Dr. MichaelGollob, a clinical arrhythmia specialist and geneticist who heads theArrhythmia Research Lab affiliated with the Institute’s CanadianCardiovascular Genetics Centre(TM).
Atrial Fibrillation is the most common form of cardiac arrhythmia(irregular beat). AF is a rapid, irregular fluttering of the heart’s beatcaused by random electrical discharges. Instead of pumping effectively, thecondition can allow blood to pool and clot in the heart, and sometimes cantrigger a stroke. In the U.S., more than 3.0 million people and in Canadasome 250,000 people are estimated to have persistent AF. AF increases therisk of stroke significantly and is responsible for more than 75,000strokes in the U.S. at a cost of more than US$1 billion.
It is known that defective genes can be inherited and can lead tofamilial disease. However, it has not been well established that mutationsduring in-utero development (somatic mutation) can also trigger disease.Noting that cases of familial AF are rare, the researchers hypothesizedthat cases of AF for which there is no obvious cause (idiopathic) might bedue to a somatic mutation confined to the heart tissue.
Dr. Gollob and colleagues focused on a gene (GJA5) which makes aprotein known as Connexin 40. The protein is specific to the atrial tissueof the heart and plays a crucial role in how electrical impulses areconducted. They discovered genetic mutations in the Connexin 40 gene in AFpatients. Researchers proved the disease was tissue-specific and notpresent in all body cells by detecting the mutation only in the hearttissue and not in the blood cells of affected patients.
Currently, AF is treated with medications that do not specificallytarget the Connexin 40 protein. A mechanical procedure called catheterablation is also employed but it is invasive and significant complicationscan arise, including stroke and death. By unlocking the mechanismresponsible for AF, it is expected that novel drug treatments that targetConnexin 40 will be developed to modify or control the disease.
“First, this study confirms that Connexin 40 plays a critical role inthe electrical conduction in the atrium of the heart,” said Dr. Gollob."Second, current medications have a moderate effect at best. These findingssuggest that drugs targeting Connexin 40 may lead to more effectivetreatment for AF. Third, it also shows that common idiopathic diseases mayhave a genetic basis with the genetic defect confined to the diseasedtissue.”
“This is a significant development in understanding the causes of heartdisease,” said Dr. Robert Roberts, President & CEO. “We salute theimpressive accomplishment of Dr. Gollob and his team and note the importantcontribution of the Canadian Cardiovascular Genetics Centre.”
About UOHI
The University of Ottawa Heart Institute is one of the largest heartcentres in North America dedicated to the prevention, diagnosis, treatment,rehabilitation, research and education of cardiovascular disease. Annually,UOHI serves over 76,000 outpatients, more than 6,000 inpatients, and analumnus of some 10,000 patients. UOHI is also home to the CanadianCardiovascular Genetics Centre(TM), an emerging international leader andthe first in Canada dedicated to mapping, identifying and determining thefunction of genes responsible for heart disease. For more information,visit http://www.ottawaheart.ca.
SOURCE UNIVERSITY OF OTTAWA HEART INSTITUTE