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Large European study finds gene variant is no strong risk factor for osteoporosis

21.02.2006


Variations in a number of different genes and environmental factors affect an individual’s risk for osteoporosis. Several gene variants have been linked to osteoporosis, but few have stood the test of time. The GENOMOS study, a large European collaboration led by Andre Uitterlinden (Erasmus University Medical Center), John Ioannidis (University of Ioannina), and Stuart Ralston (University of Edinburgh), now shows that a top candidate gene plays a role in osteoporosis, but with effects that are less marked than those described in previous studies.



The so-called Sp1 polymorphism in the COL1A1 gene is a plausible candidate: the gene contains the genetic information to make type 1 collagen, a major component of bone, and preclinical studies suggested that one of the two variants (the T version) led to weaker bones. Earlier genetic studies had found an association between the T variant and low bone mineral density (BMD) and fractures, prompting some scientists to suggest that genetic testing of people for this variant could help in assessing fracture risk. The GENOMOS study was done to evaluate how good the COL1A1 genetic test was at predicting fractures and to determine if it was associated with osteoporosis.

Over 20,000 people took part in GENOMOS, and the number of fractures reported was five times greater than in all previous studies combined. The researchers conducted genetic testing for the COL1A1 variation in participants and measured bone mineral density in all of them. The link between the T variant and osteoporosis was less impressive than that found in many earlier studies. The Sp1 polymorphism in COL1A1 was associated with reduced BMD, but the effects were small and limited to people who carried two copies of the T variant. The investigators found an association between the T variant and spine (vertebral) fractures, but there was no association with non-spine fractures. Overall, the researchers estimate that the presence of the T allele would explain at most 10% of the risk of vertebral fractures for women.


From these results, it seems clear that genetic testing for the COLIA1 variant in isolation would be premature and would not be sufficient to accurately identify people at risk of fractures. It is likely that researchers will need to develop tests that involve studying the variants in several genes (and possibly other variants in the COL1A1 gene) and use them in combination with standard methods of risk assessment such as BMD measurements, before they can usefully predict a substantial fraction of an individual’s risk for osteoporosis.

Andrew Hyde | EurekAlert!
Further information:
http://www.plosmedicine.org

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