Over the past few years, researchers have identified several mutant genes that cause potentially fatal heart rhythm irregularities, or arrhythmias. Fortunately, these mutants are rare. But now a team has discovered that a new variation in one of those genes, called SCN5A, may increase the risk of arrhythmia in members of the population at large.
In an effort to find out whether SCN5A might play a broader role in causing heart disturbances, Mark Keating of Children's Hospital and Harvard Medical School in Boston and his colleagues, including Igor Splawski, also at Children's, examined the gene in people hospitalized with heart arrhythmias. They found a particular change--a substitution of a single letter of the genetic code that changes just one amino acid in the SCN5A protein--in an African-American woman. Her heart problems could not be linked to any of the known mutations, raising the possibility that this SCN5A variation might somehow contribute to the irregularity.
Subsequent screening of the general population showed that the variant is widespread among blacks. It turned up in about 19% of 468 West Africans and Caribbeans and in 13% of 205 African Americans. In contrast, the researchers found it in just one of 123 Hispanics, and none of 511 Caucasians or 578 Asians they studied. Moreover, the team reports in the 23 August issue of Science, the variant is far more common in African Americans being treated for arrhythmias than in healthy controls, suggesting that it increases risk.
They identified a potential mechanism, too. The SCN5A protein forms a sodium channel in heart muscle cells. When appropriately stimulated, the channels open, sodium ions flow in, and the muscle cells contract. By adding the variant channel to human cells, the team found that a small percentage of the variant channels reopen at a time when they are supposed to be closed. That change could make the heart more prone to developing arrhythmias. Keating notes, however, that the differences weren't large, and that the variant alone isn't likely to cause problems.
Even so, the discovery is “important and significant,” says arrhythmia researcher Arthur Moss of the University of Rochester Medical Center in New York state. Numerous medications, including some antihistamines and blood pressure drugs, have been linked to an increased risk of arrhythmias, he says, and people carrying the variant may be more likely to experience that side effect. If that turns out to be the case, it would be relatively easy to devise a test to identify the carriers, who could then avoid the risky medications.