A gene may determine whether a postmenopausal woman responds to estrogen therapy with an increase in high-density lipoprotein cholesterol
 

A specific allele seems to determine the response of high-density lipoprotein cholesterol to postmenopausal estrogen therapy, according to an article in the March 28th issue of the New England Journal of Medicine. The finding could help doctors identify women most likely to experience cardiovascular benefit from hormone replacement therapy.

"If our findings hold true, a simple gene test could help doctors and women make better decisions about the use of hormone replacement therapy for prevention of heart disease," said David Herrington, M.D., lead author..

In an analysis of 309 women with known heart disease who took hormone replacement therapy or placebo, Herrington found that women with a common allele (variant of the gene) for the estrogen receptor alpha gene had dramatic increases in high-density lipoprotein cholesterol.

"The increase in high-density lipoprotein cholesterol was more than twice as much as in women without the gene variant," said Herrington.

These findings are important because most researchers believe an increased level of high-density lipoprotein cholesterol is the basis for prevention of heart disease, especially in older women.

Herrington found that 18 percent of women had the allele that gave them an apparent genetic predisposition to high levels of high-density cholesterol when taking estrogen. The increase in cholesterol level was dramatic: It was two or three times what is normally achieved with cholesterol drugs used to raise high-density lipoprotein cholesterol.

"More research is needed to see if the higher high-density lipoprotein cholesterol levels translate into fewer heart attacks," said Herrington. "We also need to know if women with the gene variant are more sensitive to estrogen's other effects. But, this finding is exciting because it shows the potential for doctors to use genetic testing to improve decisions about drug therapy."

This article joins others that report a genetic basis for the effects of medications such as cholesterol-lowering agents and antihypertensive drugs.

"Previous studies of cholesterol drugs show that raising high-density lipoprotein cholesterol to this extent might reduce heart disease events by 25 to 40 percent," said Herrington. "Studies with estrogen haven't shown the same connection between high-density lipoprotein cholesterol raising and heart disease benefit, but it's possible this was because we were focusing on all women, rather than the sub-group with this gene variant."

The findings of the current research may account for the variance in previous studies that evaluated the effects of hormone replacement therapy on prevention of heart disease as measured by myocardial infarction rate or other cardiac outcome.

"Our research suggests that genetics may identify some women who respond more favorably to hormone replacement therapy than others," said Herrington.

He said additional research is needed to learn if the presence of the estrogen receptor allele also makes women more sensitive to other beneficial and negative effects of postmenopausal estrogen therapy.

"… if findings such as this are confirmed in other studies, it's likely that testing for gene variants will soon become a regular part of the practice of medicine," said Herrington.


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