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Estrogen receptor glitch tied to cardiovascular disease in men
By Cheryl Simon Silver

Estrogen is commonly associated with women's health but a team of researchers reports that men with a common genetic variation in an estrogen receptor gene, called ESR1, have three times the risk of heart disease as men without the variation.

The somewhat surprising findings indicate that estrogen receptors, which are activated by estrogen in the blood, clearly play an important role in men's susceptibility to heart disease.

“In general people don't think of men even having estrogen, yet alone of estrogen receptor variation showing promise as a cardiovascular disease risk factor in men,” says Amanda Shearman, of MIT's Center for Cancer Research and lead author of the study. She says that the of role estrogen receptor genes seems to be important in increasing understanding of cardiovascular disease.

Shearman studied heart disease in 1739 unrelated individuals who are part of the on-going Framingham Heart Study. The participants in the study were 60 years old, on average. Among them, 54 men suffered a heart attack or other serious cardiovascular event, whereas only five women were similarly stricken. Generally, cardiovascular disease affects women later in life than men. There were too few events in the women to make any conclusions either positive or negative regarding association of ESR1 gene with heart attacks in women.

The study makes headway toward confirming prior observations of an association between coronary artery disease and defects in the ESR1 c.454-397CC estrogen receptor.

An editorial accompanying the article in the Journal of the American Medical Association, lauds the incremental contribution of the research. Nonetheless, its subtitle “Shedding Light into a Murky Pool” hints how difficult it is to find markers that connect a gene to likely development of disease.

One fifth of the participants carried the ESR1 gene. After the researchers adjusted their data for other risk factors such as age, sex, body mass index, hypertension, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and cigarette smoking, the presence of this gene was still associated with major heart disease.

The findings may help solve a paradox surrounding combination estrogen therapy and a woman's susceptibility to developing heart disease. Observational studies suggest that women who begin oral estrogen therapy just before menopause begins or soon after it starts have reduced risk of developing heart disease. However, heart disease is more likely in women who begin oral estrogen therapy later in menopause and after a longer period of estrogen deficiency.

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Shearman, A. et al. Association between Estrogen Receptor a Gene Variation and Cardiovascular Disease. JAMA. 2003; 290: 2263-2270.


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