Gene Variant Is Said to Be Linked To Heart Attack and Prevention

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The Wall Street Journal

Gene Variant Is Said to Be Linked To Heart Attack and Prevention
By RON WINSLOW
January 22, 2008; Page D3

Researchers said they identified a genetic variant that is linked to both an increased risk of a heart attack and a person's chances of preventing such an attack by taking a cholesterol-lowering pill called a statin. The variation, in a gene called KIF6, is present in nearly 60% of the population, the researchers found. In four large studies involving a total of more than 30,000 patients, carriers of the mutation had a risk of heart attacks, strokes or death related to heart disease as much as 55% higher than those who didn't have it. The impact of the variant was independent of such conventional cardiovascular risk factors as smoking status, cholesterol levels and diabetes.

Discovery of the KIF6 variant was announced by Celera Group-Applera Corp., an Alameda, Calif., diagnostics company known for having mapped the human genome in 2000 in a high-profile race with a government-funded project. Details are reported in three studies being published Jan. 29 by the Journal of the American College of Cardiology and now available on the publication's Web site. (http://content.onlinejacc.org/current.dtl1.)

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But the KIF6 gene -- for "kinesin-like protein family member 6" -- hasn't previously been linked to heart disease, nor has it shown up in several other genome scans probing DNA for heart-disease genes. Some experts said more study is needed to confirm the findings and determine KIF6's role in evaluating and treating patients at risk for cardiovascular disease. The report is the latest in a flurry of studies linking tiny single-letter variations called single nucleotide polymorphisms, or SNPs, in a person's DNA with risk of disease. Researchers hope that such discoveries will shed light on the biology illnesses, reveal potential new drug targets, and drive the field of personalized medicine.

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For instance, in a study called Care that originally compared Bristol-Myers Squibb Corp.'s Pravachol against placebo in patients who had already had heart disease, 12.4% of KIF6 mutation carriers treated with placebo suffered heart attacks compared with 8.1% of those who didn't have the mutation. Researchers said that translated to a relative 50% increased risk after adjusting for other factors. Among KIF6 carriers who got Pravachol, there were 37% fewer heart attacks compared with placebo. Among noncarriers, there were 14% fewer heart attacks on the drug than on placebo, suggesting those with a genetic variant responded better to the drug.

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Separately, the researchers looked at DNA taken from participants in the 25,000-patient Women's Health Study at Harvard Medical School and found that the KIF6 variant was associated with a 34% increased risk of heart attacks among women. Researchers said further study of KIF6 could help identify mechanisms for how heart disease develops and possibly new targets for drugs to treat it. Bristol-Myers sponsored the original statin trials and provided access to the DNA for two of the current papers, but neither Bristol-Myers nor Pfizer funded the new analysis, which Celera paid for.


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