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Increased risk of osteoporosis associated with gene that one in five people have


About nineteen percent of people have a genetic variation that may increase susceptibility to osteoporosis, a new study reveals. Researchers at Washington University School of Medicine in St. Louis demonstrated that in women the variant gene speeds up the breakdown of estrogen and is associated with low density in the bones of the hip.

The study will be reported in the February issue of the Journal of Bone and Mineral Research and is available online.

The gene, named CYP1A1, makes an abundant enzyme that detoxifies foreign substances and also breaks down estrogen as a normal part of maintaining proper estrogen balance. Within the general population, several variations of the CYP1A1 gene exist, and the variants differ from one another by one or more DNA base pairs. "Previous studies showed that some CYP1A1 variants are linked to estrogen-related cancers, such as breast, ovarian or endometrial cancers," says Reina Armamento-Villareal, M.D., assistant professor of medicine in the Division of Bone and Mineral Diseases. "The link to estrogen suggested that the gene could also affect bone density. 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 researchers studied 156 women with an average age of 63.5 years who were at least one year past menopause. They analyzed the genetic sequence of each woman’s CYP1A1 gene to identify which of the genetic variants they possessed.

One of the variations of the gene, known to be present in 19 percent of the general population, was found in women who had significantly lower blood estrogen levels and higher levels of urinary estrogen breakdown products than normal. These women also had a higher than normal urinary concentration of a marker that indicates bone resorption and had significantly lower than normal bone density in regions of 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 serum estrogen levels and high levels of estrogen metabolites," Villareal says. "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."

The research team measured bone density in both the spine and the upper femur. The bone mass of the spine proved not to be affected by genetic variation in CYP1A1. "Our study suggests that this genetic variant specifically affects the hip bones," Villareal says. "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."

Recent statistics from the National Osteoporosis Foundation estimate that more than 20 percent of hip fracture patients die within a year. Additionally, about 30 percent of hip fracture patients will fracture the opposite hip, up to 25 percent may require long-term nursing home care and only 40 percent fully regain their prefracture level of independence.

Given the seriousness of the condition, Villareal asserts it would be very advantageous to identify those people at especially high risk for osteoporosis of the hip. The CYP1A1 variant that the researchers linked to osteoporosis may be an important genetic marker for evaluating that risk. "Ideally, you want to start early to avoid osteoporosis," Villareal says. "Our next study will look at a much younger group of women. My guess is that we will find that females with this variant gene are breaking down estrogen rapidly from the day they are born. In that case, they would never achieve an adequate peak bone density and would lose even more bone mass after menopause. If we can catch them at an early age, we can maximize their chances to avoid osteoporosis."

Gwen Ericson | EurekAlert!
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