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Estrogen and heart disease in women
Association between polymorphism in estrogen receptor gene and blood pressure
Edward R. Winstead

The risk of heart disease increases among women after menopause. Many studies report that estrogen hormone therapy can reduce the risk of cardiovascular disease for some women, but the data are inconsistent. A 1998 study found that replacement hormones offered no protection against heart attack for nearly 3,000 postmenopausal women with coronary artery disease. To some observers, the surprising result underscored how little is really known about the role of estrogen in cardiovascular health.

Women possessing the 26-repeat motif had elevated blood pressure.

The effects of estrogen, whatever they may be, are likely to be mediated through receptors on the walls of blood vessels. Two estrogen receptor genes—ERa and ERb—have been identified. In 1993, researchers found an association between ERa and hypertension. A new study by researchers in Japan reports an association between a variant of ERb and elevated blood pressure. The researchers speculate that the variant, or polymorphism, may play a role in causing hypertension in Japanese women.

A group of postmenopausal Japanese women with a form of ERb had significantly higher systolic blood pressure than did others in the study. ERb contains two letters of genetic code that are repeated at varying length in different individuals. The number of 'dinucleotide' repeats among subjects in the study ranged from 18 to 32, and women possessing the 26-repeat motif had the elevated blood pressure levels.

The study, which appears in the Journal of Human Genetics, is among the first to examine associations between polymorphisms in ERb and blood pressure. The researchers previously reported an association between the dinucleotide polymorphism in ERb and high bone mineral density.

In the current study, Sumito Ogawa and Satoshi Inoue, of the University of Tokyo, and colleagues determined the number of dinucleotide repeats in ERb for 187 healthy, postmenopausal women between the ages of 61 and 91. A series of blood pressure readings were taken, and the researchers sorted and analyzed the data. The differences in pressure among the women occurred only in systolic blood pressure. (Systolic pressure is measured as the heart contracts to pump out the blood; diastolic pressure is measured as the heart relaxes to allow the blood to flow into the heart.)

The molecular mechanism behind the association remains unknown. The study's sample population was relatively small, and the researchers write in their paper that more study of the polymorphism in additional populations is needed. Hypertension is a predictor of cardiovascular disease, and the rationale for the study was to begin to clarify genetic risk factors for the diagnosis, prevention, and ultimately treatment of hypertension.

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Ogawa, S. et al. Association of estrogen receptor b (ESR2) gene polymorphism with blood pressure. J Hum Genet 45, 327-330 (2000).

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