An extended family living in the American mid-west state of Iowa has helped scientists to find the first gene that unequivocally causes heart attacks in late middle-age.
The family has an extensive history of heart attacks with the risk highest at about the age of 60. A heart attack becomes almost inevitable in members of the family who have inherited a defect in a gene known to be involved in the formation of blood vessels.
Eric Topol of the Cleveland Clinic Foundation in Ohio said that although the genetic defect has only been found in this family, its discovery could lead to a better understanding of heart attacks in the general population. "This stands out because of its potential impact. It's a great first step towards understanding the basis of coronary artery disease at its genetic roots," Dr Topol said. "We have learnt from other genetic studies that once you get the first gene it starts to unlock the whole story."
Interest in the Iowa family began when one of its members, a 61-year-old man who suffered a heart attack, told doctors that eight of his 10 siblings also had heart attacks at about the same age.
Doctors eventually traced 26 close family members with heart problems. The researchers took blood samples for DNA analysis in the hope of finding a common genetic link to the disorder.
The study found that a region of chromosome 15 - one of the 23 pairs of chromosomes in the human genome - contained a linkage "hotspot" that was known from previous studies to include a gene called MEF2A.
The gene is involved in the repair and maintenance of artery walls and the research team found that the family members who had suffered heart attacks also possessed a deletion mutation within the MEF2A gene.
None of their relatives, or 119 other, unrelated individuals without heart problems, possessed the same defect. This suggested that the defect causes the build-up of fatty deposits inside the vital arteries supplying nutrients to the heart.
Dr Topol said the immediate benefit would be to develop a test that could identify people within the same family who are carrying the defective gene. "There are 100 members of this family. We can tell now in kids aged 10 whether they have the heart attack gene or not."
Other factors, such as smoking, increase the chances of an earlier heart attack for those people carrying the defect but the total avoidance of an attack is not possible, he said. "We're not talking about an increased risk. If you're not run over by a truck or get another disease first, you're going to have a heart attack," he said.