Exp Mol Med.
2006 Oct;38(5):519-524.
Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women
- Affiliations
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- 1Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
- 2Department of Genetic Epidemiology, SNP Genetics, Inc. Seoul, Korea.
- 3Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea. epark@knu.ac.kr
- 4Department of Pathology, School of Dentistry, School of Medicine, Kyungpook National University, Daegu, Korea.
- 5Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
Abstract
- Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P=0.002). That is, the highest osteocalcin levels (34.5+/-16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6+/-14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8+/-10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.
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