A gene found in some people of African descent may slightly increase the chance that they will experience an irregular heartbeat, or arrhythmia, which can be lethal in rare cases. Most people with this gene will never experience an arrhythmia, but some may benefit from taking certain precautions, say the study authors. The U.S. and U.K. team reports its findings in the journal Science, published by the American Association for the Advancement of Science.
Approximately 450,000 people die suddenly each year in the United States of arrhythmia, which is a variation in the heartbeat's rate or rhythm. In most cases, this is the outcome of a heart attack or another heart condition, but arrhythmia can also happen spontaneously.
In their Science study, Mark Keating of Children's Hospital, in Boston, Harvard Medical School, and Howard Hughes Medical Institute, and his colleagues calculated that people with the so-called "Y1102" variation of a certain heart gene have an eight times greater risk of arrhythmia. Keating cautioned, however, that the incidence of arrhythmia is so low for any individual, even an eight-fold increase in risk does not mean he or she is likely to experience one.
"We've identified one variant, which is one piece in a huge puzzle. But, every time we can identify a piece, we can use that information to reduce risk, which is already quite low for an individual at any given moment," Keating said.
The gene variation, or "allele," doesn't cause life-threatening arrhythmia on its own, but it might help to cause one in people lacking enough electrolytes--potassium, calcium, sodium, and magnesium--in their blood serum. Certain drugs including diuretics, commonly taken to reduce blood pressure, reduce electrolyte levels, as does strenuous exercise.
"It's important to make sure that serum electrolytes stay normal. We do things all the time that make them abnormal, such as taking diuretics, or running marathons," Keating said.
Precautionary measures might include using alternatives to diuretics, and making sure to drink a lot of water or a sports drink during strenuous exercise, Keating said.
"Basically you just need to balance things," he said.
Electrolytes are essential for helping the heart muscle contract. In the muscle cells that induce the contraction, various electrolyte ions spill in through specialized channels on the cell surface. This generates a message, or "action potential," that propagates from one cell to another.
The authors identified the allele by comparing DNA samples from people with "non-familial" cardiac arrhythmia, which is the more common form of the disorder, rather than the rare form that is passed down in a few families. They looked for variations in certain genes they knew to be associated with arrhythmia, from previous studies of the less common "familial" forms. The researchers also studied DNA samples from a set of "controls," who weren't known to have arrhythmia.
Keating's team found that many of the individuals with arrhythmia had the Y1102 variation in a gene that encodes part of the channel regulating the flow of sodium in and out of heart muscle cells. Cells with these channels should be slightly more excitable than normal, the researchers concluded from their experiments.
This effect increased when the researchers simulated the effects of having low electrolyte levels, the Science study reports.
Among the control group, the authors found the Y1102 allele in 19.2 percent of the people from West Africa and the Carribbean, 13.2 percent of African Americans, not in any Caucasians or Asians, and in one of 123 Hispanics.
Next, they looked at 23 African Americans with arrhythmia, and 100 healthy African Americans, and found that the allele was disproportionately common among arrhythmia cases. The researchers also studied the extended family of one African American individual with arrhythmia. Eleven out of 23 members had related heart irregularities, and all 11 had the Y1102 allele.
Researchers have discovered a number of genes involved in arrhythmia, but thus far they have been associated with mutations in rare familial disorders. This is the first to involve a relatively large portion of the population, Keating said.
The other authors of the study are Igor Splawski and Alan H. Beggs, of Children's Hospital and Harvard Medical School, in Boston, MA; Katherine W. Timothy and Alka Malhotra, of the University of Utah, in Salt Lake City, UT; Michihiro Tateyama, Colleen E. Clancy, and Robert S. Kass of Columbia University, in New York, NY; Francesco P. Cappuccio and Giuseppe A. Sagnella at St. George's Hospital School in London.
The study was supported by the NIH.