Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification.

• Osteoporosis is a major health problem affecting more than 75 million people throughout Europe, USA and Japan. Epidemiological studies have determined that both genetic and environmental factors contribute to the pathogenesis of osteoporosis. We have investigated the association between polymorphisms at the osteocalcin locus and variables linked to bone health. Osteocalcin provides a link between bone and energy metabolism, hence its potential importance as an osteoporosis candidate gene. In this study, we included a total of 996 women (all aged 75 years) from the OPRA cohort. We sequenced the osteocalcin gene along with flanking region to search for novel coding polymorphisms. We also analyzed four polymorphisms selected from within and flanking regions of the osteocalcin gene to study their association with serum total osteocalcin levels (S-TotalOC), total body (TB) bone mineral density (BMD), fracture, TB fat mass and BMI. The promoter polymorphism rs1800247 was significantly associated with S-TotalOC (p = 0.012) after controlling for BMI and TB BMD. The polymorphism rs1543297 was significantly associated with prospectively occurring fractures (p = 0.008). In a model taking into account rs1543297 and rs1800247 along with TB BMD, BMI, smoking and S-TotalOC, the polymorphisms together were able to identify an additional 6% of women who sustained a fracture (p = 0.02). We found no association between the polymorphisms and TB BMD, BMI or TB fat mass. In conclusion, polymorphisms in and around the osteocalcin locus are significantly associated with S-TotalOC and fracture. Genotyping at the osteocalcin locus could add valuable information in the identification of women at risk of osteoporosis. (c) 2010 American Society for Bone and Mineral Research.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Ortopedi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Orthopaedics (hsv//eng)

Publication and Content Type

art (subject category)

ref (subject category)