Increased risk of osteoporosis associated with gene that 1 in 5 people have

[Guest guest]

Medical News Today 02 Feb 2005

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. "

Napoli N, Villareal DT, Mumm S, Halstead L, Sheikh S, Cagaanan M, Rini GB,

Armamento-Villareal R. The effect of CYP1A1 gene polymorphisms on estrogen

metabolism and bone density. Journal of Bone and Mineral Research, 2005

Feb;20(2):232-9.

Funding from the National Institutes of Health supported this research.

----------

Internal Virus Database is out-of-date.

Checked by AVG Anti-Virus.

Version: 7.0.300 / Virus Database: 265.6.12 - Release Date: 01/14/2005