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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.

Citation

Duk Jae Kim, Byung Lae Park, Jung-Min Koh, Ghi Su Kim, Lyoung Hyo Kim, Hyun Sup Cheong, Hyoung Doo Shin, Jung-Min Hong, Tae-Ho Kim, Hong-In Shin, Eui Kyun Park, Shin-Yoon Kim. Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women. Experimental & molecular medicine. 2006 Oct 31;38(5):519-24

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PMID: 17079868

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