[Paleopsych] NYT: Genetic Find Stirs Debate on Race-Based Medicine

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Genetic Find Stirs Debate on Race-Based Medicine
http://www.nytimes.com/2005/11/11/health/11heart.html

    By NICHOLAS WADE

    In a finding that is likely to sharpen discussion about the merits of
    race-based medicine, an Icelandic company says it has detected a
    version of a gene that raises the risk of heart attack in
    African-Americans by more than 250 percent.

    The company, DeCode Genetics, first found the variant gene among
    Icelanders and then looked for it in three American populations, in
    Philadelphia, Cleveland and Atlanta.

    Among Americans of European ancestry, the variant is quite common, but
    it causes only a small increase in risk, about 16 percent.

    The opposite is true among African-Americans. Only 6 percent of
    African-Americans have inherited the variant gene, but they are 3.5
    times as likely to suffer a heart attack as those who carry the normal
    version of the gene, a team of DeCode scientists led by Dr. Anna
    Helgadottir reported in an article released online yesterday by Nature
    Genetics.

    Dr. Kari Stefansson, the company's chief executive, said he would
    consult with the Association of Black Cardiologists and others as to
    whether to test a new heart attack drug specifically in a population
    of African-Americans.

    The drug, known now as DG031, inhibits a different but closely related
    gene and is about to be put into Phase 3 trials, the last stage before
    a maker seeks the Food and Drug Administration's approval.

    Last year a drug called BiDil evoked mixed reactions after it was
    shown to sharply reduce heart attacks among African-Americans, first
    in a general study and then in a targeted study, after it failed to
    show efficacy in the general population. The drug, invented by Dr. Jay
    N. Cohn, a cardiologist at the University of Minnesota, prompted
    objections that race-based medicine was the wrong approach.

    Geneticists agree that the medically important issue is not race
    itself but the genes that predispose a person to disease. But it may
    often be useful for physicians to take race into account because the
    predisposing genes for many diseases follow racial patterns.

    The new variant found by DeCode Genetics is a more active version of a
    gene that helps govern the body's inflammatory response to infection.
    Called leukotriene A4 hydrolase, the gene is involved in the synthesis
    of leukotrienes, agents that maintain a state of inflammation.

    Dr. Stefansson said he believed that the more active version of this
    gene might have risen to prominence in Europeans and Asians because it
    conferred extra protection against infectious disease.

    Along with the protection would have come a higher risk of heart
    attack because plaques that build up in the walls of the arteries
    could become inflamed and rupture. But because the active version of
    the gene started to be favored long ago, Europeans and Asians have had
    time to develop genetic changes that offset the extra risk of heart
    attack.

    The active version of the inflammatory gene would have passed from
    Europeans into African-Americans only a few generations ago, too short
    a time for development of genes that protect against heart attack, Dr.
    Stefansson suggested.

    The DG031 drug being tested by DeCode Genetics affects a second gene,
    but one that is also involved in control of leukotrienes. Because the
    drug reduces leukotriene levels and inflammation, it may help
    African-Americans who have the variant of the hydrolase gene. "It
    would make scientific, economic and particularly political sense to
    have a significant part of the clinical trials done in an
    African-American population," Dr. Stefansson said.

    A spokeswoman for the black cardiologists' group, which supported the
    BiDil trial, said the group's officials were not ready to discuss the
    new gene.

    Dr. Troy Duster of New York University, an adviser to the federal
    Human Genome Project and a past president of the American Sociological
    Association, said he saw no objection to a trial, provided it focused
    on African-Americans with the risk-associated variant of the gene and
    took into account that people with ancestry from different regions of
    Africa might show variations in risk.

    But Dr. Charles Rotimi, a genetic epidemiologist at Howard University,
    said a separate study of African-Americans would not be desirable. The
    variant gene may be overactive in African-Americans because of their
    greater exposure to deleterious environments, Dr. Rotimi said.

    Dr. Cohn, the inventor of BiDil, said it was "always best to study a
    drug in a highly responsive group," rather than testing large
    populations where possible benefits to subgroups could be missed.