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Survival of heart patients on beta-blockers varies greatly with genetic variation

to relieve stress on the heart. They also block impulses that can cause rhythm disturbances.

"Long-term therapy with beta-blockers is standard care for heart patients," Lanfear says. "Data from patients with acute myocardial infarction have shown that beta-blockers are generally effective. They are known to decrease the size of the infarct and seem to prolong survival, on average."

Recent research, however, reveals that variations in the beta-adrenergic receptor genes affect the benefit of beta-blockers in heart patients. Data indicate that variations of the genes influence such parameters as blood pressure response in hypertensive patients and heart function in heart failure patients.

"But this is the first time that anyone has shown that these genetic variations affect survival," McLeod says.

Humans have two types of beta-adrenergic receptors, beta-1 and beta-2. In this study, the researchers found no difference in survival associated with variations of the beta-1 gene. But variations in the beta-2 gene significantly determined length of survival for ACS patients who were taking beta-blockers. For those patients not taking beta-blockers, variations in the beta-adrenergic receptor genes showed no evidence of effect on survival, although small sample size makes this result uncertain.

The beta-2 gene commonly has two points of sequence variation within the human population--for most of the population, the gene's coding sequence will be identical from person to person at all other points. Thirty-nine percent of the population possess a set of beta-2 genes with a C base at position 79, and 16 percent possess at set of beta-2 genes with an A base at position 46.

In this study, ACS patients on beta-blockers with either of these two specific genetic variations constituted the high-risk group--by the end of three years, 20 percent of this group had died. By comparison, patients who had G bases at position 79 or 46 on both
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Source:Washington University School of Medicine


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