Osteoporosis linked with common gene

About 19 percent of people have a genetic variation that may increase susceptibility to osteoporosis, according to a School of Medicine study.

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

The gene, CYP1A1, makes an abundant enzyme that detoxifies foreign substances and breaks down estrogen as a normal part of maintaining estrogen balance.

Within the general population, several variations of the CYP1A1 gene exist, and the variants differ 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,” said Reina Armamento-Villareal, M.D., assistant professor of medicine.

“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 people — was found in women who had significantly lower than normal blood estrogen levels and higher levels of urinary estrogen breakdown products.

These women also had a high urinary concentration of a marker that indicates bone resorption and had significantly lower than normal bone density in regions of the upper femur.

“The data suggest that this 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 said.

“Low levels of estrogen put women 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 said. “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 Na-tional 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.

Villareal said it would be very advantageous to identify 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.

“Our next study will look at a much younger group of women,” she said. “My guess is that we’ll find females with this variant gene are breaking down estrogen rapidly from the day they are born. In that case, they’d never achieve 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.”