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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