NEW YORK (Reuters Health) - For the first time, a genetic mutation in the myocyte enhancer factor-2 (MEF2) family of transcription factors has been linked to familial coronary artery disease, researchers at the Cleveland Clinic report. The MEF2 protein is normally involved in vascular morphogenesis and is strongly expressed in coronary artery epithelium.
Previous research has identified four susceptibility loci for coronary artery disease (CAD), Dr. Qing Wang and colleagues note in their article in the November 28th issue of Science.
Dr. Wang’s group studied a large family with 13 patients who displayed an autosomal dominant pattern of CAD, and found a significant linkage to a locus on chromosome 15, which includes the gene encoding MEF2A. Their analysis revealed a 21-base pair deletion in all 10 affected family members who were still alive.
Immunofluorescence staining showed that the defective MEF2A product was retained in the cytoplasm of human umbilical vascular endothelial cells and human aortic smooth muscle cells, whereas wild-type was localized to the nucleus. The defective gene had only a third of the normal transcription activity.
In an interview with Reuters, co-author Dr. Eric Topol described the mutation as “a deletion that affects coronary artery walls, making them less able to protect themselves from plaque buildup and heart disease.”
People with the exact genetic mutation of the Iowa family have a 100 percent chance of having a heart attack or developing coronary artery disease, Dr. Topol said.
“For them, it’s not a matter of ‘if,’ it is a matter of ‘when.’ For that reason, we think this specific mutation will prove to be rare,” he added.
The gene deletion was not found in three other large families with CAD and in 50 sporadic patients. Therefore, Dr. Topol expects that other genetic alterations associated with CAD “will be more common and not carry as high a risk.”
Nevertheless, the group’s findings identify a genetic pathway and molecular mechanism that could be important in the pathogenesis of CAD and MI, the authors conclude.
Source: Science 2003;302:1578-1581. [ Google search on this article ]
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