Fat and Obesity Gene also Affects Hip Fracture: 82
Percent Risk Increase for Women
Women in study all over 60, bone health was followed
between 1989 and 2007; during period, 102 had hip fractures
25, 2013 - Australian researchers have demonstrated a strong association
between the FTO (fat and obesity) gene and hip fracture in
women. While the gene is already well known to affect diabetes and body
fat, this is the first study to show that its high-risk variant can
increase the risk of hip fracture by as much as 82%.
The study, undertaken by Dr Bich Tran and Professor
Tuan Nguyen from Sydneys Garvan Institute of Medical Research, examined
six gene variants (single nucleotide polymorphisms, or SNPs) of the
FTO gene, taken from the DNA of 934 women in the Dubbo Osteoporosis
Epidemiology Study (DOES). The women were all over 60, and their bone
health was followed between 1989 and 2007. During that period, 102 women
had hip fractures.
On average, the risk of fracture is about 11%. The
study showed that if a woman has a low-risk genotype, or gene variant,
the risk of fracture is 10%. If she has a high-risk genotype, it is 16%.
Now published online in
Clinical Endocrinology, the
authors believe that the findings have the potential to improve
prediction of hip fracture. Known risk factors, also to be taken into
account, include advancing age, falls, history of fracture, low bone
mineral density, low body mass index (BMI) and genetic make-up.
We found that for a woman of the same age and same
clinical risk factors, those with the high-risk genotype have an
increased risk of fracture of 82% - a very high effect in genetic
terms, said Professor Tuan Nguyen.
A genome-wide association study published in 2007
suggested that genetic variants in the FTO gene were associated
with variation in BMI. This led us to hypothesise that they might also
be associated with variation in hip fracture risk.
The present study tested our hypothesis by
examining the association between common variants in the FTO gene
and hip fracture.
Our results showed a strong association with hip
fracture, with some gene variants doubling the risk of fracture.
Interestingly, this was independent of both the bone density and BMI of
the women we studied.
We also found that the FTO gene expresses
in bone cells, and may have something to do with bone turnover, or
remodelling, although its exact mechanisms are unclear.
Its important to emphasise that, while promising,
our finding is a first step. It will need to be replicated in other
studies, and its mechanisms clearly understood before it is useful in
At Garvan, we developed a Fracture Risk Calculator
several years ago,
using algorithms based on data from the Dubbo study. The calculator,
which is fairly accurate and easy to use, is very popular with patients
In the future, I would anticipate that genetic
risk factors including this finding would be programmed into the
calculator, making it an even more finely-tuned predictive tool.
The Garvan Institute of Medical Research was
founded in 1963. Initially a research department of St Vincent's
Hospital in Sydney, it is now one of Australia's largest medical
research institutions with over 600 scientists, students and support
staff. Garvan's main research areas are: Cancer, Diabetes & Obesity,
Immunology and Inflammation, Osteoporosis and Bone Biology and
Neuroscience. Garvan's mission is to make significant contributions to
medical science that will change the directions of science and medicine
and have major impacts on human health. The outcome of Garvan's
discoveries is the development of better methods of diagnosis,
treatment, and ultimately, prevention of disease.
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