Genes Explain Race Disparity in Response to a Heart Drug

Doctors who treat patients with heart failure have long been puzzled by a peculiar observation. Many black patients seem to do just as well if they take a mainstay of therapy, a class of drugs called beta blockers, as if they do not. It is almost as if they were immune to the drugs.

Now researchers at Washington University and the University of Maryland have discovered why: these nonresponsive patients have a slightly altered version of a gene that muscles use to control responses to nerve signals. People with this altered gene are making what amounts to their own version of beta blockers all the time. As many as 40 percent of blacks and 2 percent of whites have the gene variant, the researchers report.

The findings, heart failure specialists say, mean that people with the altered gene might be spared taking what may be, for them, a useless therapy. And since patients with heart failure typically take multiple drugs, which can interact and cause side effects like fatigue, getting rid of a drug that is not helping can be a huge benefit.

This is the first time anyone has found such a gene effect, said Dr. Stephen Liggett, a heart failure and genetics researcher at the University of Maryland and one of the first authors of the study.

"Conceptually, this is quite a surprise," Dr. Liggett said.

Equally surprising is how common the altered gene is, especially among black patients.

"Something that occurs with a 40 percent frequency is not something that was a blip on the radar screen," said Dr. Gerald W. Dorn, a cardiologist at Washington University and principal investigator for the study. "It must have given a survival advantage."

But he has no idea yet what that advantage might be.

A paper describing the results of the research was published on the Web site of the journal Nature Medicine on April 20.

The discovery raises questions about whom to treat with beta blockers and how to decide, researchers say. But, they add, its implications go beyond heart failure.

For example, the gene variant may help explain why some healthy people cannot exercise vigorously -- they may be making chemicals that act like beta blockers, making their hearts beat less forcefully. And variations in other genes might explain why some people with different conditions, like depression, do not respond to drugs used to treat it. It is possible that those people are already making their own versions of antidepressant drugs, and that adding more may not help. ...

•	Genes Explain Race Disparity in Response to a Heart Drug The New York Times, Tuesday, April 29, 2008 Byline: Gina Kolata

	Story also ran in 5 others:  International Herald Tribune (France), Tuscaloosa News (AL), eMaxHealth.com (NC), BlueRidgeNow.com (NC) and Gainesville Sun (FL)