Published: February 8, 2012
Although heart disease is the leading killer of women as well as of men, two heart disease patients out of every three are male, and heart disease strikes men 10 to 15 years earlier than it does women. No one really knows why.
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Health Guides: Heart Attack | Atherosclerosis
Now, a new study reports that part of the answer may lie on the Y chromosome, the one chromosome unique to men.
In the study, published on Wednesday in The Lancet, researchers found that nearly all British men have one of two variants of a cluster of genes on their Y chromosome. Those with one of the variants had a 50 percent increased risk of heart disease compared with men with the other variant. This risk was independent of traditional factors like cholesterol, smoking and diabetes.
The study needs to be replicated, researchers say, and while it raises intriguing hypotheses, it is not definitive.
The researchers also do not yet know which individual genes in the cluster are responsible for the increased risk, nor do they know why the genes have this effect. And the study, said its lead author, Dr. Maciej Tomaszewski of the University of Leicester, does not completely explain the male disadvantage in heart disease.
But Virginia M. Miller, a heart disease researcher at the Mayo Clinic in Rochester, Minn., who wrote an editorial that accompanied the paper, said in an interview that the work “puts a whole different perspective on some risk factors for heart disease in men.”
Everyone knows men who did all the wrong things — ignored their cholesterol levels, smoked — and yet were spared heart disease, Dr. Miller said. And everyone knows men who were careful about their diet, controlled their cholesterol levels and blood pressure and did not smoke, yet died young from heart attacks.
The message of the new study, Dr. Miller said, was that for some of those unlucky men, “yes indeed, they did have inheritable factors that independently caused death.” And when a screening test is developed to find those Y chromosome gene clusters and researchers have a better understanding of how they act, it may be possible to protect some of them from having heart attacks.
Dr. Tomaszewski and his colleagues found the Y chromosome gene association by looking at men in two large British heart disease studies. He said he and his colleagues were surprised by the magnitude of increase in risk for men with one of two genetic clusters.
Dr. Daniel J. Rader, a heart disease researcher at the University of Pennsylvania, said it was also possible that simply having a Y chromosome instead of two X chromosomes, as women have, increased heart disease risk. The extra X could be protective.
Dr. Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital, said it was strange that there had been almost no study of the Y chromosome’s effect on heart disease. Although the reasons were technical, having to do with the way gene searches were done, ignoring the Y, he said, “was a little bit of an oversight.”
Heart disease researchers have generally ignored the role of the Y chromosome, assuming it was mostly involved in determining maleness, Dr. Tomaszewski said. He suggested the cluster of genes on the Y chromosome of the men with lower risk may help control inflammation, a process that is part of the formation of atherosclerotic plaques.
Others were less convinced. “A lot more work needs to be done” on the gene cluster, Dr. Rader said.
Dr Kathiresan said the association between the gene cluster and heart disease risk needed to be confirmed.
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