LRP5 Gene Variants Linked To BMD and Fracture Risk


Variants in the LRP5 gene are associated with both bone mineral density and fracture risk, researchers reported in JAMA.

Two LRP5 variants were found to have “modest” effects that were very consistent across different populations and independent of subject sex or age. Based on these findings, carriers of these polymorphisms may have a fracture risk that is 15%–20% higher than that for noncarriers, wrote Joyce van Meurs, Ph.D., of Erasmus Medical Center, Rotterdam, the Netherlands, and her associates in the Genetic Markers for Osteoporosis (GENOMOS) consortium.

The study involved 37,534 subjects who underwent genotyping and assessment of bone mineral density. A total of 8,932 subjects had fractures, including 2,146 vertebral fractures (JAMA 2008;299:1277–90).

Members of the GENOMOS consortium—18 research teams in Europe and North America—performed prospective genotyping for several polymorphisms of the LRP5 gene that are thought to be related to osteoporosis. “Some scattered studies have tested this association, but results have not been conclusive due to limited sample size,” the researchers wrote.

“The current collaborative study has the potential to answer this question more definitively because of its large sample size and therefore large power to observe the expected modest associations,” Dr. van Meurs and her associates explained.

“Although any single marker explains only a small portion of the phenotype risk, identification of several such osteoporosis risk variants may eventually help in improving clinical prediction,” they wrote. “Single genetic risk variants may also offer useful insights about mechanisms and pathways that may be useful in drug development.”

The investigators cautioned that their results may not apply to Asian or African populations, since the study subjects were predominantly whites of European descent.

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