Researchers from the Howard Hughes Medical Institute at Children's Hospital in Boston say that a variant form of a gene found in the heart muscle of some African-Americans may increase the chances of developing a potential deadly heart condition called cardiac arrhythmia.

The researchers estimate that 4.6 million African-Americans carry this gene variant. The finding could benefit African-Americans by making it possible to detect who is at increased risk for developing arrhythmia and allowing those affected to take preventive measures. The study is one of the first in which researchers have been able to discern how genetics influences arrhythmia risk across a range of populations of people who originated from different geographic regions.

The research team led by HHMI investigator Mark T. Keating reported that 13.2 per cent of African-Americans in the study carried an altered form of the gene SCN5A. This gene codes for a protein called a sodium channel, a molecular pore that initiates heartbeats by allowing sodium to flow across the membrane of the cardiac muscle cell.

The variant form of the gene creates sodium channels in heart muscle cells that remain open longer than normal sodium channels, prolonging contraction of the heart and contributing to arrhythmia.

Keating emphasized that although arrhythmias are serious disorders, the effect of the gene variant is subtle.

Keating does not believe that routine testing is warranted. The test is fairly simple and inexpensive, so many people may elect to have it, if and when it becomes commercially available, he said. Those most likely to seek testing are people whose medical condition or medications might make them vulnerable to arrhythmias. Currently the test is available only as part of a research study.

In beginning their search for polymorphisms (gene variants) that might contribute to arrhythmia, Keating and his colleagues started with the gene SCN5A because mutations in that gene were known to play a role in rare inherited arrhythmia disorder, called long QT syndrome, that can cause sudden death.

In their initial studies, the scientists found the same polymorphism, which they named Y1102, in several patients with arrhythmias that did not appear to run in their families. Their studies showed that changing one nucleotide in the SCN5A gene resulted in a sodium channel that carried an alteration in a single amino acid.

A broader survey of several population groups revealed that the Y1102 polymorphism occurred in 19.2 percent of people of West Africans and Caribbean descent, and in 13.2 percent of African-Americans studied. However, the gene variant was not found in Caucasians or Asians, and in only one of 123 Hispanics.

Keating and his colleagues also found that the Y1102 polymorphism occurred disproportionately in African-American patients with arrhythmia and in all phenotypically affected members of one African-American family.

The scientists also conducted cell culture studies that revealed how the Y1102 variant affected the sodium channel by subtly altering its "gating," causing it to remain open slightly longer, which prolongs action potential duration and increases the excitability of cardiac muscle cells. This effect could cause transient conduction abnormalities between heart cells, contributing to arrhythmia risk. Finally, the scientists compared a computer simulation of the effects of Y1102 with actual clinical findings of drug effects on arrhythmia, discovering that the polymorphism did produce the predicted sensitivity.

While the researchers hope their findings will benefit people who have the Y1102 variant, they also emphasize the broader implications of their discovery. The research was partially funded by the National Heart, Lung, and Blood Institute.