Follow Our Live Coverage of COVID-19 Developments

Gene Variation Raises Heart Attack Risk

But researchers find association only in men

Please note: This article was published more than one year ago. The facts and conclusions presented may have since changed and may no longer be accurate. And "More information" links may no longer work. Questions about personal health should always be referred to a physician or other health care professional.

HealthDay Reporter

TUESDAY, Nov. 4, 2003 (HealthDayNews) -- A common genetic variation related to an estrogen receptor seems to be associated with a threefold greater risk of having a heart attack.

A new study adds, however, that this association has been found only in men. While the researchers looked for a similar link in women, the evidence in this study was inconclusive.

There are two known estrogen receptors, ESR1 and ESR2, which are found in both men and women.

Estrogen receptors, which are activated by the hormone estrogen, regulate genes for several risk factors for cardiovascular disease in both men and women.

While variations occur in the DNA sequence of the ESR1 and ESR2 genes, it's not known if this affects risk for heart disease.

The authors of a study appearing in the Nov. 5 issue of the Journal of the American Medical Association set out to see if there was a connection between a particular ESR1 variant and various heart problems.

They followed 875 men and 864 women who were children of the original Framingham Heart Study participants from 1971 to 1998, to see who developed heart disease. The Framingham Heart Study is a landmark epidemiological study that began in 1948. None of the participants in the current study were related. The participants also provided blood samples from which DNA was extracted.

As it turned out, 20 percent of the participants shared a particular variation on both copies of the chromosome that carries the ESR1 gene. These people also had three times the incidence of heart attacks compared with the rest of the group.

"In the study, similar to the general population, most of the people who had heart attacks by around age 60 were men," says study author Amanda M. Shearman, a research scientist in the department of biology at the Massachusetts Institute of Technology in Cambridge. "All it means is that the results are significant in men, and we can't say if it is or isn't in women. It's inconclusive in women."

The absolute risk of having a heart attack by around 60 years of age was 12 percent of men with the "high-risk" genotype.

The implication (for men) is that ESR1 may have a role in the developing of atherosclerosis and/or in speeding the transition from early atherosclerosis to outcomes such as heart attacks.

The findings do provide more evidence as to the importance of estrogen receptors in susceptibility to cardiovascular disease, especially in men. They may also one day help to explain the conflicting data regarding the effects of hormone therapy on susceptibility to heart disease in women. "The findings themselves may not help to explain it, but the findings may provide a rationale that will allow us to explain it if we do more studies," Shearman says.

While the finding does confirm previous observations, it does not prove any cause-and-effect relationship and has little practical implication as of yet. If anything, says Dr. Paul N. Hopkins, a professor of internal medicine at the University of Utah School of Medicine in Salt Lake City and co-author of an accompanying editorial, the article highlights the "whole issue of the complicated nature and imperfections and limitations in genetic testing, illustrates how far we are from making anything useful of it."

The variant also does not have a "huge, glowing, dramatic effect," Hopkins adds, which means that there may be several different genes and gene variations involved.

Still, he adds, the study is "encouraging. I wouldn't write it off to statistical fluke."

These researchers, however, have miles to go before they sleep and one crucial task is to see if the findings can be generalized to other groups, including women. "It's important to see if these results actually hold up in other populations," Shearman says.

"I would suspect that one day we will have to have a big consortium of investigators that have lots of cases of coronary disease and lots of controls and can apply lots of genes -- something that has a mass genomic approach rather than one gene at a time," Hopkins says. "There are just too many genes that people are talking about."

In the meantime, keep in mind that many risk factors for heart disease can be modified with lifestyle changes such as exercising and eating well. "Even small improvements in a few of these things can have a good effect on heart health," Shearman says.

More information

The American Heart Association has more on estrogen and heart disease in women and on heart attacks.

SOURCES: Amanda M. Shearman, Ph.D., research scientist, department of biology, Massachusetts Institute of Technology, Cambridge, Mass.; Paul N. Hopkins, M.D., professor, internal medicine, University of Utah School of Medicine, Salt Lake City; Nov. 5, 2003, Journal of the American Medical Association

Last Updated: