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Gene Variant Ups Osteoporosis Risk

One in five may carry the estrogen-linked mutation

TUESDAY, Feb. 8, 2005 (HealthDay News) -- About one in five people carry a variant of a gene that may increase their risk for osteoporosis, researchers report.

When found in women, a variant of the CYP1A1 gene appears to speed the breakdown of the female hormone estrogen, which normally helps protect women against bone loss. Women with the gene mutation were more prone to with low bone density at the hips, according to researchers at the Washington University School of Medicine in St. Louis.

The study appears in the February issue of the Journal of Bone and Mineral Research.

There are several variations of the CYP1A1 gene, which makes a enzyme that detoxifies foreign substances in the body and also breaks down estrogen as part of maintaining proper estrogen balance.

"Previous studies showed that some CYP1A1 variants are linked to estrogen-related cancers, such as breast, ovarian or endometrial cancers," researcher Dr. Reina Armamento-Villareal, an assistant professor of medicine in the division of bone and mineral diseases, said in a prepared statement.

"The link to estrogen suggested that the gene could also affect bone density," she explained. "No one had ever investigated that possibility, so we set up a study to evaluate the relation between bone density and variations of the CYP1A1 gene."

The study included 156 postmenopausal women averaging 63.5 years of age. The genetic sequence of each woman's CYP1A1 gene was analyzed to determine which variant they had.

One variant, found in 19 percent of the population, was found in women with much lower blood estrogen levels and higher levels of urinary estrogen breakdown products than normal. The women with this variant also had much lower bone density in the upper femur near the hip joint.

"The data suggest that this particular variation of the gene produces an enzyme that breaks down estrogen faster than usual, leading to low [blood] estrogen levels and high levels of estrogen metabolites. Low levels of estrogen put a woman at risk for osteoporosis, and our data showed a strong correlation between the genetic variant and low bone density," Villareal said.

"Our study suggests that this genetic variation specifically affects the hip bones. For those with this form of the CYP1A1 gene, that's not good news. Low density in the hip can lead to hip fractures, which can be devastating," Villareal said.

This variant may prove a useful genetic marker for early identification of females with a high risk of osteoporosis of the hip, enabling them to receive a head start on treatment to prevent osteoporosis.

More information

The American College of Rheumatology has more about osteoporosis.

SOURCE: Washington University School of Medicine, news release, Feb. 1, 2005
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