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Risk gene for osteoporosis discovered

(Vienna, 21 July 2010) An interdisciplinary working group headed by Ao. Univ. Prof. Dr. Gerold Holzer and Univ. Prof. DI Dr. Christine Mannhalter, who both work at MedUni Vienna, has been able to prove that the connection between vitamin K and bone density can be negatively influenced by mutations in a recently discovered gene. This finding could change future therapy decisions for affected risk groups.

Around 75 million people worldwide currently suffer from osteoporosis, a largely genetically determined disease which is characterised by low bone density and a deteriorated microarchitecture of the bone tissue. Fractures often occur as complications of osteoporosis and lead to concomitant diseases with high mortality. This is counteracted by vitamin K, which stimulates bone metabolism, leads to higher bone density and can reduce fractures.

The team headed by Holzer, Department of Orthopaedics, and Mannhalter, Division of Medical and Chemical Laboratory Diagnostics, has now been able to show in a study for the first time that patients with a specific genotype have a significantly higher bone density than people of another genotype. Mutations in the vitamin K epoxide reductase gene (VKORC1 gene) evidently play a key role here. The gene product of VKORC1 is, as an enzymatic catalyst, partly responsible for the regeneration of "used" vitamin K and the formation of functionally active osteocalcin. Osteocalcin is a protein which plays a decisive role in bone building, and as a blood marker also gives information about whether bone tissue is developed.

A mutated VKORC1 gene cannot ensure sufficient formation of functionally active vitamin K and osteocalcin and therefore aids the development of osteoporosis. The current study has been able to show that patients with the genotype 9041 AA have both a "more active" VKORC1 gene and also a higher amount of functional osteocalcin than patients of another genotype (AG or GG). People with the "AA genotype" have much less chance of becoming ill with osteoporosis. This connection was revealed for the first time at MedUni Vienna and in the future may influence how individual treatment is provided for osteoporosis patients.

The authors say the following about the possible effects of the study: "We think that our results justify carrying out major studies to show the advantage of genetic analysis as a basis for individualised choice of therapy."


The study was recently published in "Translational Research, The Journal of Laboratory and Clinical Medicine" under the title "Vitamin K epoxide reductase (VKORC1) gene mutations in osteoporosis".
(G Holzer, AV Grasse, S Zehetmayer, P Bencur, Ch Bieglmayer, Ch Mannhalter Vitamin K epoxide reductase (VKORC1) gene mutations in osteoporosis: A pilot study.
Translational Research, The Journal of Laboratory and Clinical Medicine 2010; 156: 37-44)