Feb. 8, 2012 -- Move over, estrogen. There's a new theory that helps explain why men are more likely than women to get heart disease.

A new study shows that some men may inherit a higher risk for heart disease directly from their fathers.

The finding is significant in the world of genetics because it ties heart disease risk to the male Y chromosome. Previous studies have suggested that the Y chromosome, which carries relatively few genes, has little to do with inheritance beyond conferring male sex characteristics.

“It gives a completely new role for the Y chromosome,” says Lisa Bloomer, MSc, who made the discovery as a third-year PhD student in the department of cardiovascular sciences at the University of Leicester in the U.K. “It changes a lot of how we see genetics and the sex chromosomes and how important they are.”

A Visual Guide to Heart Disease
The Y Chromosome and Heart Disease

For the study, which is published in The Lancet, an international team of researchers analyzed DNA from more than 3,000 men in the U.K.

In particular, they looked at 11 regions on the Y chromosome. Because the Y chromosome has not changed much over time, scientists can use these regions to determine a person’s ancestry. In genetics, people with shared ancestry belong to the same haplogroup. There are thought to be about 30 haplogroups worldwide.

Researchers found that men who developed heart disease were more likely to belong to the same haplogroup -- haplogroup I -- compared to men who stayed healthy. In fact, being a member of haplogroup I raised a man’s risk for heart disease by about 50% compared to men of different backgrounds.

That risk remained even after researchers took into account traditional risk factors for heart disease like high blood pressure, cholesterol, smoking, diabetes, and obesity.

Haplogroup I was the third most powerful predictor that men would develop heart disease, behind their HDL, or “good,” cholesterol levels, and whether or not they were taking cholesterol-lowering drugs. Experts estimate that about 20% of men in Europe and 10% of men in the U.S. belong to haplogroup I.

Finding May Explain Geographic Differences in Heart Disease

The lineage is more commonly found in northern European countries, like Denmark, Norway, and Sweden, and it becomes less frequent in southern countries including Spain, France, and Italy.

“You see kind of a gradient in Europe between the North and the South,” Bloomer says. “Many more people in the North have this group than in [the] South, and you have many more people getting coronary artery disease in the North of Europe than in the South.”

Beyond the association between heart disease and haplogroup, researchers went one step further. They looked to see if the activity of certain blood cells was different between ancestral groups. They found that genes related to the development of atherosclerosis -- hardening of the arteries -- were more active in men who belonged to haplogroup I. There were other key differences related to inflammation and immune function.

“The sex chromosomes matter in terms of disease,” says Virginia M. Miller, PhD, a professor of physiology and surgery at the Mayo Clinic in Rochester, Minn.

Miller, who studies sex differences in heart disease, wrote a commentary on the new findings, but she was not involved in the research.
For Men, Father’s Heart Disease History May Be an Underappreciated Risk

She says the new findings mean that family history may be a stronger predictor of heart disease risk for men than for women.

“You may have a family history, but this paper says it matters if it’s from your father’s side and you’re a man,” she says.

Some heart disease risk calculators, like the widely used Framingham Risk Score, don’t account for family history or whether it comes from the mother’s or father’s side, she says. If further research confirms the findings of this study, Miller thinks they will probably need adjusting.

“We need to broaden our scope in terms of what is the individual risk and really personalize it for people in terms of managing their own health,” she says.